E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C Virus Infection |
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E.1.1.1 | Medical condition in easily understood language |
Hepatitis C Virus Infection |
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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 | 14.1 |
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 |
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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 |
1) To evaluate the efficacy of each treatment arm of MK-5172 in combination with RBV as assessed by the proportion of subjects achieving SVR12 (Sustained Virologic Response 12 weeks after the end of all study therapy), defined as HCV RNA <25 IU/mL (either TD(u) or TND) 12 weeks after the end of all study therapy.
2) To evaluate the safety and tolerability of MK-5172 in combination with RBV. |
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E.2.2 | Secondary objectives of the trial |
1)Evaluate the efficacy of each treatment arm of MK5172 in combination w\RBV as assessed by the time to 1st achievement of undetectable (TND) HCV RNA
2)Evaluate the efficacy of each treatment arm of MK5172 in combination w\RBV as assessed by the proportion of subjects achieving undetectable (TND) HCV RNA and HCV RNA <25 IU/mL at Wk 2, Wk 4, Wk 12 and at the end of treatment visit
3)Evaluate the efficacy of each treatment arm of MK5172 in combination w\RBV as assessed by the proportion of subjects achieving:
•SVR4 (Sustained Virologic Response 4wks after end of all study therapy), defined as HCV RNA <25 IU/mL (either TD(u) or TND) 4wks after the end of all study therapy
•SVR24 (Sustained Virologic Response 24wks after end of all study therapy), defined as HCV RNA <25 IU/mL (either TD(u) or TND) 24wks after end of all study therapy
4)Evaluate the emergence of viral resistance-associated variants (RAV) resistant to MK5172 when administered as part of a combination regimen w\RBV |
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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 |
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E.3 | Principal inclusion criteria |
In order to be eligible for participation in this trial, the subject must:
1. be ≥18 years of age on day of signing informed consent.
2. have a body weight >50 kg (111 lbs) and ≤ 125 kg (275 lbs).
3. be IL28B CC genotype
4. have chronic, compensated HCV GT 1 infection as defined by:
Positive serology for HCV with HCV RNA levels ≥ 10,000 IU/mL in peripheral
blood at screening, and
Absence (no medical history or physical findings) of ascites, bleeding esophageal
varices, hepatic encephalopathy, or other signs or symptoms of advanced liver
disease, or cirrhosis
5. have had no evidence of cirrhosis and/or hepatocellular carcinoma. This can be confirmed either by liver biopsy or by non-invasive methods such as fibrotest or fibroscan in countries where biopsy is not the standard method of diagnosis.
6. 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 male subject with female sexual partner who is of childbearing potential).
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E.4 | Principal exclusion criteria |
Subject will be excluded from participating in the trial if the subject:
1) has a non-GT 1 HCV infection, including a mixed GT infection (with a non-GT 1) or a non-typeable genotype.
2) is NOT treatment naïve, i.e. subject has had previous treatment with any interferon, ribavirin, approved or experimental direct acting antiviral(s), or other investigational therapies for HCV.
3) As determined by documented records, subject is HIV positive or known to be coinfected with hepatitis B virus (HBsAg positive).
4) has evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC.
5) has pre-existing psychiatric condition(s)
6) has any known medical condition that could interfere with the subject’s participation in and completion of the trial
7) has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years
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
9) is a male whose female partner(s) are pregnant
10) has exclusionary laboratory values as listed in the protocol
i) Hemoglobin <12 g/dL for females and <13 g/dL for males.
ii) Neutrophils <1.5 x 103/μL (<1.2 x 103/μL for Blacks).
iii) Platelets <150 x 103/μL
iv) Direct bilirubin >1.5 x ULN (upper limit of normal) of the laboratory reference range
v) Serum glucose:
- For subjects not previously diagnosed with diabetes mellitus, ≥ ULN mg/dL (fasting) unless HbA1c ≤ 7%.
- For subjects previously diagnosed with diabetes mellitus, HbA1c > 8.5%.
vi) PT/PTT values > 10% above laboratory reference range
vii) Anti-nuclear antibodies (ANA) > 1:320
viii) ALT > 350IU/L
ix) AST > 350 IU/L |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the proportion of subjects achieving SVR12 in each treatment arm. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
SVR12 (12 weeks after completion of therapy) |
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E.5.2 | Secondary end point(s) |
1. the time to first achievement of undetectable (TND) HCV RNA;
2. the proportion of subjects achieving undetectable (TND) HCV RNA and HCV RNA < 25 IU/mL at Week 2, Week 4, and Week 12 and End of Treatment visit.
3. the proportion of subjects achieving SVR4 and SVR24.
4. the emergence of antiviral resistance to MK-5172 when administered as part of a combination regimen with RBV |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
please see E.5.2 for a descritption of each secondary endpoint and timepoint of evaluation. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
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 |
Australia |
Israel |
New Zealand |
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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
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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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |