| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| 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 |
| The primary objective of this study is to evaluate the efficacy of SCH 503034 800 mg TID PO in combination with PegIntron 1.5 µg/kg QW SC plus ribavirin (800-1400 mg QD PO) in previously untreated adult CHC subjects infected with Genotype 1. |
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| E.2.2 | Secondary objectives of the trial |
1. To evaluate the safety of SCH 503034 when used in combination with PegIntron 1.5 µg/kg QW SC plus ribavirin (800-1400 mg QD PO).
2. To assess the relationship of a) early virologic response (EVR) and b) time to HCV-RNA negative, to sustained virologic response (SVR).
3. To assess the effect of the 4 week lead in with PegIntron and ribavirin on SVR (FW 24).
4. To assess the effect of duration of treatment with SCH 503034 on SVR.
5. To assess the proportion of subjects with HCV-RNA levels below the limit of detection at FW 12.
6. To assess the proportion of subjects with HCV-RNA levels below the limit of detection at 72 weeks post randomization.
7. To explore the relationship between virologic response at FW 12, FW 24 (SVR), and 72 weeks post randomization.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject must be between 18 and 60 years of age;
2. Subject’s body weight must be between 45 and 125 kg;
3. Subject must have documented chronic hepatitis C genotype 1 with most recent (within 6 months of Day 1) quantitative HCV-RNA result greater than or equal to 10,000 IU/mL;
4. Subject must have a liver biopsy within 5 years of Day 1 with histology consistent with chronic hepatitis and no other etiology for chronic liver disease. A copy of the local pathology report must be available in the site’s file;
5. Subject and subject's partner(s) must each agree to use acceptable methods of contraception 2 weeks prior to Day 1 and at least 6 months or longer if dictated by local regulations after last dose of study drug (see Section 7.6.1).
6. Subjects must be willing to give written informed consent
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| E.4 | Principal exclusion criteria |
1. Subjects who received prior treatment for hepatitis C
2. Subjects known to be co-infected with HIV or hepatitis B virus (HBsAg positive)
3. Evidence of decompensated liver disease as specified in the protocol
4. Diabetic and hypersensitive subjects with clinically significant ocular exam findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other clinically significant abnormality
5. Pre-existing psychiatric condition as specified in the protocol
6. Clinical diagnosis of substance abuse of the following drugs within the following timeframes (not including time spent in detoxification, hospitalization, or incarceration):
a. Alcohol, intravenous drugs, inhalational (not including marijuana), psychotropics, narcotics, cocaine use, prescription or over-the-counter drugs: within 1 year of the Screening visit.
b. Multi-drug abuse (2 or more substances in 6a): within 3 years of Screening visit OR
Subjects receiving opiate agonist substitution therapy within 1 year of Screening visit
OR
Subject’s historic marijuana use is deemed excessive by the Principal Investigator (or physician listed on FDA Form 1572) or is interfering with the subject's life, then the subject is not eligible. If subject's marijuana use is not deemed excessive and does not interfere with life, subject must be instructed to discontinue any current use of recreational marijuana prior to entry into study and throughout the study period
7. Any known pre-existing medical condition that could interfere with the subject’s participation in and completion of the study as specified in the protocol.
8. Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated basal cell carcinoma of the skin)
9. Subjects who are pregnant or nursing. Subjects who intend to become pregnant during the study period. Male subjects with partners who are, or intend to become, pregnant during the study period
10. Any other condition which, in the opinion of the Principal Investigator, or physician listed in FDA Form 1572 would make the subject unsuitable for enrollment or could interfere with the subject participating in and completing the study.
11. Participation in any other clinical trial within 30 days of the screening visit or intention to participate in another clinical trial during participation in this 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).
12. Treatment with any investigation drug within 30 days of screening visit in this study.
13. Subjects who are part of the site personnel directly involved with this study.
14. Subjects who are family members of the investigational study staff.
Laboratory Exclusion Criteria
NOTE: If any of the laboratory exclusion criteria are met, then the site may have the subject retested. If a single value is more than 10% outside the listed laboratory exclusion criterion value, the clinical significance of this value may be discussed with the sponsor’s Project Physician for enrollment consideration.
15. Hematologic, biochemical, and serologic criteria (growth factors may not be used to achieve study entry requirements:
a. Hemoglobin <12 g/dL for females and <13 g/dL for males
b. Neutrophils <1500/mm3 (Blacks: <1200mm3)
c. Platelets <100,000/mm3
d. Direct Bilirubin >1.5 x ULN (upper limit of normal) of the laboratory reference range. Total bilirubin >1.6 mg/dL unless history if Gilbert’s disease. If Gilbert’s disease is the proposed etiology, this must be documented in the subject’s chart.
16. Serum albumin <LLN (lower limit of normal) of laboratory reference range
17. Thyroid stimulating hormone (TSH) >1.2 x ULN or <0.8 x LLN of laboratory reference range (subject can use thyroid medication to be in an acceptable TSH range and subject must be clinically euthyroid)
18. Serum creatinine >ULN of the laboratory reference range unless calculated creatinine clearance is > 100 mL/min as calculated by the Cockroft-Gault formula: CrCl [mL/min] = [140 – age in years] x actual weight (kg)/serum creatinine [µmol/L]. Multiply result by 1.2 for males
19 Serum glucose:
a. For subjects not previously diagnosed with diabetes mellitus;
1. >126 mg/dL (non-fasting) unless HbA1c < 7% OR
2. >110 mg/dL (fasting) unless HbA1c < 7%
b. For subjects previously diagnosed with diabetes mellitus, HbA1c > 8.5%
20. PT/PTT values >10% above laboratory reference range
21. Anti-nuclear antibodies (ANA) > 1:320
22. Alpha fetoprotein (AFP):
a. AFP>100 ng/mL OR
b. AFP 50 to 100 ng/mL requires liver ultrasound with no evidence of hepatocellular carcinoma
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the achievement of SVR, defined as plasma HCV-RNA level below the lower limit of detection at follow-up week 24 (FW 24). Subjects will be declared treatment failures in one of the following ways:
- Subjects in any of the 5 treatment arms who are HCV-RNA positive at FW 24.
- Subjects in any of the 5 treatment arms who are missing their HCV-RNA level at FW 24 and are not HCV-RNA negative at FW 12.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| 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 | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
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| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 22 |
| 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 | Information not present in EudraCT |
| 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 |
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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 | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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