E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
A viral infection affecting the liver |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the efficacy of MK-5172 + MK-8742 in HCV GT1 subjects
with chronic kidney disease (CKD) within the immediate treatment and the intensive
PK groups.
• To evaluate the safety and tolerability of MK-5172 in combination with
MK-8742 in the immediate treatment group relative to the placebo treatment of the
deferred treatment group. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of MK-5172 in combination with MK-8742 as assessed by the proportion of subjects achieving:
-SVR24 within the immediate treatment and the intensive PK groups, defined as HCV RNA <LLoQ (either TD(u) or TND) 24 weeks after the end of all study therapy.
- SVR4, defined as HCV RNA <LLoQ (either TD(u) or TND) 4 weeks after the end of all study therapy.
-SVR12, defined as HCV RNA <LLoQ (either TD(u) or TND) 12 weeks after the end of all study therapy on active period of deferred treatment arm,
- SVR12, defined as HCV RNA <LLoQ (either TD(u) or TND) 12 weeks after the end of all study therapy for all active treatment arms combined.
To evaluate the safety and tolerability of MK-5172 in combination with MK-8742 for all treatment arms.
To evaluate the emergence of viral RAVs resistant to MK-5172 and MK-8742 when administered as part of a combination
regimen. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trials. Such research is for biomarker testing to adress emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is ti use such information to develop safer, more effective drugd, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time. |
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E.3 | Principal inclusion criteria |
1. Be ≥18 years of age on day of signing informed consent. 2. Have documented chronic (at least 6 months) HCV GT1 infection (with no evidence of non typable or mixed genotypes) : • Positive for anti-HCV antibody, HCV RNA, or an HCV genotype • HCV RNA (≥ 10,000 IU/mL in peripheral blood) 3.Subjects with or without cirrhosis may be enrolled into this study. All subjects must have one of the below liver disease staging assessments as follows: • Liver biopsy performed within 24 months of Day 1 (if subject is cirrhotic then there is no time restriction on biopsy) • Fibroscan performed within 12 months of Day 1 • A FibroSure® (Fibrotest®) and Aspartate Aminotransferase to Platelet Ratio Index (APRI) (APRI is automatically calculated by central laboratory) during Screening In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above critieria, a liver biopsy is required. Liver biopsy results supersede the results obtained by Fibroscan or FibroSure®. 4. Have an HCV treatment status that is one of the following: Treatment naïve: Naive to all anti-HCV treatment Prior IFN or PEG-IFN + Ribavirin Treatment failures: Null responders, Partial responders, Relapsers. P/R Intolerant: Subjects were intolerant to a prior IFN or PEG-IFN ± Ribavirin regimen, Subjects discontinued treatment prematurely and were therefore unable to complete a full course of therapy because of drug-related toxicity. 5. Have Chronic Kidney Disease defined as: Subjects with GFR ≤29 who are non-dialysis dependent (NDD) or have been on hemodialysis (HD) for at least 3 months (including subjects awaiting kidney transplant and subjects with failed kidney transplants no longer on immunosuppressant therapy). 6. Agree (if subject is of reproductive potential) to remain truly abstinent or use (or have their partner use) 2 acceptable methods of birth control from at least 2 weeks prior to Day 1 and through 14 days after the last dose of study drugs, or longer if dictated by local regulations. If acceptable by local regulatory agencies, methods of birth control allowed in the study are: intrauterine device (IUD), diaphragm with spermicide, hormonal contraceptives (e.g., birth control pills, transdermal patch, or injectables), contraceptive sponge, female condom, male condom with spermicide or vasectomy. 7. A female subject who is not of reproductive potential is eligible without requiring the use of contraception. A female subjects who is not of reproductive potentials is defined as one who has either 1) reached natural menopause (defined as 12 months with no menses without an alternative medical cause), 2) 6 weeks post surgical bilateral oophorectomy with or without hysterectomy, or 3) bilateral tubal ligation. 8. A male subject who is not of reproductive potential is eligible without requiring the use of contraception. A male subject who is not of reproductive potential is defined as: one who has undergone a successful vasectomy. A successful vasectomy is defined as: (1) microscopic documentation of azoospermia, or (2) a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post vasectomy. 9. understand the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent. 10. 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 |
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E.4 | Principal 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, in the opinion of the investigator, would interfere with the study procedures. 2. Evidence of decompensated liver disease manifested by the presence of or history of ascites, gastric or variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease. 3. Is on peritoneal dialysis for management of Kidney disease 4. In the opinion of the investigator the subject has a high likelihood of receiv ing a renal transplant during the study treatment period (up to 24 weeks from Day 1). 5. Is coinfected with hepatitis B virus (e.g. HBsAg positive) or HIV. 6. 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 has evidence of hepatocellular carcinoma (HCC) or is under evaluation for other active or suspected malignancy. 7. Is taking or plans to take any of the prohibited medications listed in Section 5 of this protocol within 2 weeks of Day 1. 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. has a clinical diagnosis of substance abuse of the following specified drugs within specified timeframes: • alcohol, intravenous drugs, inhalational (not including marijuana), psychotropics, narcotics, cocaine use, prescription or over -the-counter drugs: within 1 year of the screening visit or, if shorter is judged by the investigator to be capable of complying with study procedures, OR • history of marijuana use is deemed excessive by a physician investigator or is interfering with the subject's daily function. If subject's marijuana use is not deemed excessive and does not interfere with daily function, subject must be instructed to discontinue any current use of recreational marijuana prior to entry into trial and throughout the trial period. 9. has a clinical diagnosis of substance abuse of the following specified drugs within specified timeframes: • alcohol, intravenous drugs, inhalational (not including marijuana), psychotropics, narcotics, cocaine use, prescription or over -the-counter drugs: within 1 year of the screening visit or, if shorter is judged by the investigator to be capable of complying with study procedures, OR • history of marijuana use is deemed excessive by a physician investigator or is interfering with the subject's daily function. If subject's marijuana use is not deemed excessive and does not interfere with daily function, subject must be instructed to discontinue any current use of recreational marijuana prior to entry into trial and throughout the trial period. 10. Female subject who is pregnant or breast-feeding, or expecting to conceive or donate eggs from Day 1 and through 14 days after the last dose of study drugs, or longer if dictated by local regulations or male subject who is expecting to donate sperm from Day 1 and through 14 days after the last dose of study drugs, or longer if dictated by local regulations. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The SVR12 rate of the subjects in the immediate treatment and intensive PK arms |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. the SVR4 and SVR24 rates of the subjects within the immediate treatment and the intensive PK arms.
2. the SVR4 , SVR12 and SVR24 rates in the deferred treatment arm following the end of all active study therapy
3. the SVR4 , SVR12 and SVR24 rates following the end of all active study therapy for all treatment arms combined
4. the emergence of viral resistance to MK-5172 and MK-8742 when administered as a combination regimen
5. the proportion of subjects achieving TND, TD(u) and TD(q) at end of treatment
6. the PK endpoints for MK-5172, MK-8742 are AUC0-24, C2hr and Ctrough.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After administration, SVR4 , SVR12, SVR24 and End of Treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Canada |
Estonia |
France |
Israel |
Korea, Republic of |
Lithuania |
Netherlands |
Spain |
Sweden |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |