| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Hepatitis C Virus Genotype 2, 4, 5 and 6 |
|
| E.1.1.1 | Medical condition in easily understood language |
| Hepatitis C Virus Infection |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10019744 |
| E.1.2 | Term | Hepatitis C |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10047457 |
| E.1.2 | Term | Viral hepatitis C |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 |
Part A:
In treatment naïve (TN) patients with chronic GT2 HCV infection with pre-treatment HCV RNA of at least 10,000IU/mL;
1. To evaluate whether a combination treatment regimen of study drugs, MK-5172 + MK-8742 + Ribavirin, are safe and effective in reducing the amount of Hepatitis C virus in the blood after 12 weeks of end of study treatment.
Part B:
In treatment naïve(TN)non-cirrhotic subjects with chronic HCV infection with GT2, 4, 5 or 6:
1. To evaluate whether the treatment of MK-5172 in combination with or without MK-8742 and/or RBV, are safe and effective in reducing the amount of hepatitis C virus in the blood after 12 weeks of end of study treatment.
|
|
| E.2.2 | Secondary objectives of the trial |
Part A:
In treatment naïve (TN) patients with chronic GT2 HCV infection with pre-treatment HCV RNA of at least 10,000IU/mL;
1. To evaluate whether the study drugs have the ability to reduce the level of Hepatitis C virus to a level that becomes undetectable. This will be assessed after 4 weeks and 24 weeks of end of study treatment.
2. To evaluate whether the Hepatitis C virus has the ability to develop resistance against the antiviral study drugs.
Part B:
In treatment naïve (TN) patients with chronic GT2, GT4, GT5 and GT6 HCV infection
1. To evaluate the effect in each treatment arm of MK-5172 with/without MK-8742 and/or RBV in reducing the amount of hepatitis C virus in the blood after 12 weeks end of study treatment.
2. To evaluate the effect in each treatment arm of MK-5172 with/without MK-8742 and/or RBV of proportion of subjects achieving undetectable HCV RNA levels at week 2, week 4 and week 12 end of treatment.
3. To evaluate the effect of the study medic |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
In order to be eligible for participation in this trial, the subject must:
The following applies to both Part A and Part B (unless specified otherwise)
1. be at least 18 years of age on day of signing informed consent.
2. have a body weight above 50 kg (111 lbs) and below 125 kg (275 lbs).
3. For Part A only: have Chronic Hepatitis C Virus infection; specifically genotype 2. The amino acid variant at position 31 in the NS5A region must be documented prior to enrollment of the study.
For Part B only: have chronic Hepatitis C virus GT2 or GT4, or GT5 or GT6 infection.
- Positive for antiHCV antibody, HCV RNA or an HCV genotype at least 6 months before screening and positive for HCV RNA more than 10,000 IU/mL in blood at the time of screening.
- Absences of ascites, bleeding esophageal varices, hepatic encephalopathy or other signs or symptoms of advanced liver disease or cirrhosis.
4. absence of cirrhosis, defined as any one of the following:
- Liver biopsy performed within 2 years of day 1 of this study showing absence of cirrhosis.
- Fibroscan (in countries where locally approved) performed within 12 months of day 1 of this study with a result of <12.5 kPa
5. agree to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations (for female subject who is of childbearing potential or 2 weeks prior to day 1 and continue until at least 7 months after last dose of study drug for male subject with female sexual partner who is of childbearing potential).
6. understand the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
7. provide written informed consent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. |
|
| E.4 | Principal exclusion criteria |
The subject must be excluded from participating in the trial if the subject:
The following criteria apply to both Part A and Part B (unless specified otherwise)
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. For Part A: has non genotype 2 Hepatitis C Virus infection, including a mixed GT infection or a non-typeable genotype.
For Part B: has HCV infection with a genotype other than GT2, GT4, GT5 or GT6, including a mixed GT infection or infection with nontypeable genotype.
3. is not treatment naïve (has previously received treatment for Hepatitis C).
4. proven to be coinfected with hepatitis B or HIV.
5. 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 study. Collection of additional blood, urine, or tissue samples or additional data, beyond that specified in this protocol, is prohibited (other than that related to subject’s medical care).
6. has a clinical diagnosis of substance abuse.
7. has evidence of active or suspected malignancy (cancer), or a history of malignancy, within the last 5 years. Subjects under evaluation for malignancy are not eligible.
8. (female) is pregnant, lactating, expecting to conceive or donate eggs, or is of childbearing potential and unwilling to commit to two methods of birth control throughout treatment and after the completion of all treatment; or male subject is planning to impregnate or provide sperm donation or has a female sexual partner of childbearing potential and is unwilling to commit to using two methods of birth control throughout treatment and after the completion of all treatment .
9. is a male whose female partner(s) is pregnant.
10. has any other condition which, in the opinion of the principal investigator or study physician, would make the subject unsuitable for enrollment or could interfere with the subject participating in and completing the study.
11. is a member or a family member of the investigational study staff or sponsor staff directly involved with this study.
12. has evidence or history of chronic hepatitis not caused by Hepatitis C Virus.
13. For subjects diagnosed with diabetes mellitus, documented HbA1C > 8.5% to exclude uncontrolled diabetes.
14. Has exclusionary laboratory values:
Laboratory Assessment Non cirrhotic
hemoglobin < LLN (lower limit of normal) of laboratory reference range
neutrophils <1.5 x 103/μL (<1.2 x 103/μL for Blacks)
platelets <125 x 103/μL
direct bilirubin >1.5 x ULN
Total Bilirubin >1.6 mg/dL unless history of Gilbert's disease. (If Gilbert’s disease is the proposed etiology, this must be documented in the subject’s chart)
Serum Albumin < 3.5 g/dL (lower limit of normal) of laboratory reference range
creatinine clearance <50 mL/min
INR >1.5
ALT >350
AST >350
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the proportion of subjects achieving sustained virologic response (SVR12). This will be defined as HCV RNA levels <25IU/mL 12 weeks after the end of all study therapy.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 12 Weeks after the end of all study therapy. |
|
| E.5.2 | Secondary end point(s) |
Subjects samples will be analysed to assess those achieving sustained virologic response (<25 IU/mL HCV RNA levels) at 4 and 24 weeks after the end of all study therapy.
Subjects achieving undetectable HCV RNA and HCV RNA <25 IU/mL levels at Week 2, Week 4, Week 12 of the treatment period will also be assessed.
PK samples will be taken to evaluate PK concentrations, PK/PD and PK/AE relationships of MK-5172, MK-8742 and RBV. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
HCV RNA levels will be measured at weeks 2,4 and 12 during the treatment period and also weeks 4 and 24 after the end of all study therapy for viral load secondary endpoints.
PK samples will be taken for analysis at weeks 1,2,4,8 and 12 during the treatment period. |
|
| 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 | Yes |
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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 | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 5 |
| 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 |
| Belgium |
| France |
| Italy |
| New Zealand |
| Australia |
| Spain |
| Israel |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 17 |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 25 |
Print
