E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic hepatitis C |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019744 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021881 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10019805 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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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 |
The primary objective of this trial is to compare the effect on efficacy of erythropoietin use versus RBV dose reduction for the management of anemia in subjects who become anemic during the treatment of chronic hepatitis C (CHC) genotype 1 infection with boceprevir plus PEG2b/RBV therapy. |
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E.2.2 | Secondary objectives of the trial |
1) To determine the safety and tolerability of erythropoietin use versus RBV dose reduction as defined by the cumulative discontinuation rate of the two treatments. 2) To evaluate the safety of erythropoietin for the management of anemia in subjects who become anemic during combination therapy with boceprevir plus PEG2b/RBV. 3) To define predictors of SVR such as epidemiologic factors, disease characteristics, and on-treatment response during erythropoietin use versus RBV dose reduction in anemic subjects when used during combination therapy with boceprevir plus PEG2b/RBV. 4) To determine the efficacy of combination therapy with boceprevir plus PEG2b/RBV in subjects who do not become anemic during therapy. 5) To evaluate the safety of combination therapy with boceprevir plus PEG2b/RBV in subjects who do not become anemic during therapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria for CHC 1. Subject must have previously documented CHC genotype 1 infection. Subjects with other or mixed genotypes are not eligible. The HCV-RNA result obtained from the central laboratory at the Screening Visit must confirm genotype 1 infection and be ≥10,000 IU/mL. 2. Hemoglobin concentration at Screening must be ≤15 g/dL for both females and males and will be strictly observed. 3. Subject must have a liver biopsy with histology consistent with CHC and no other etiology. Copies of the pathology report and histology slides (suitable for evaluation by the trial central pathologist) are required for the subject to be included in the trial. The slides and the pathology report must be accessible by the trial site prior to Day 1. Using the Scoring Systems for Hepatic Fibrosis, the investigator must determine the level of fibrosis demonstrated by the biopsy. a. For subjects with fibrosis F0-3 the biopsy must have been obtained within 3 years of the screening visit. If the timing of the liver biopsy does not meet this criterion, the liver biopsy may be performed between Screening and Day 1 (only if the subject’s Screening Visit confirms that the subject meets the other trial inclusion criteria). b. For subjects with F4 (cirrhosis), any historic liver biopsy demonstrating cirrhosis will be accepted regardless of length of time since biopsy. Two unstained slides are preferred for reading by the central pathologist selected by the sponsor; however, one slide stained with hematoxylin plus eosin (H & E) plus one slide stained with Masson’s trichrome will be accepted (slides should be reviewed by the investigator to confirm adequacy). The central pathologist reading will be used for analysis purposes only; Day 1 procedures will be performed based upon the local report. 4. Subjects with bridging fibrosis (F3) or cirrhosis (F4) must have an ultrasound within 6 months of the Screening Visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma (HCC). 5. Subject must be ≥18 years of age. 6. Subject’s weight must be ≥40 kg and ≤125 kg. 7. Subject and subject’s partner(s) must each agree to use acceptable methods of contraception as specified for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study medication, or longer if dictated by local regulations. 8. Subjects must be willing to give written informed consent. 9. Subjects must be willing to attend frequent site visits for the duration of the trial. 10. Subjects must not have any contraindications for the use of erythropoietin. |
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E.4 | Principal exclusion criteria |
1. Coinfected with HIV or hepatitis B 2. Prior treatment for HCV; except herbal remedies, except those with hepatotoxicity. Herbal remedies must be discontinued, except silymarin 3. Any investigational drug within 30 days 4. Receiving any of the following medication within 2 weeks: alfuzosin, antiarrhythmics (amiodarone, bepridil, flecainide,propafenone, and quinidine), ergot derivatives, cisapride, lovastatin, simvastatin,pimozide, triazolam, and orally administered midazolam. 5. Participation in other clinical trial within 30 days or intention to participate during this trial. Collection of additional blood, urine, or tissue samples beyond that specified, is prohibited (unless related to the subject’s medical care) 6. Decompensated liver disease including, clinical ascites, bleeding varices, or hepatic encephalopathy 7. Diabetic or hypertensive with significant ocular examination findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other significant abnormality 8. Pre-existing psychiatric condition(s), including: a. Moderate or severe depression. b. Depression associated with: i. Hospitalization ii. Electroconvulsive therapy iii. Prolonged absence from work or significant disruption of daily functions c. Suicidal or homicidal ideation or attempt d. Severe psychiatric disorders (not limited to schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder or mania) e. Lithium use f. Antipsychotic drug use 9. Substance abuse of specified drugs within specified timeframes (not including time spent in detoxification, hospitalization, or incarceration): a. Alcohol, IV drugs, inhalational (not marijuana), psychotropics, narcotics, cocaine use, prescription or over-the-counter drugs: within 1 year b. Multi-drug abuse within 3 years c. Receiving opiate agonist substitution therapy within 1 year (unless monitored in an opioid substitution maintenance program) d. Marijuana use is excessive or interfering with daily function. Discontinue any recreational marijuana 10. Pre-existing medical condition that could interfere with participation/completion of the trial: a. CNS trauma requiring intubation, intracranial pressure monitoring, brain meningeal or skull surgery, or resulting in seizure, coma, permanent neurologic deficits, abnormal brain imaging, or CSF leak. Prior brain hemorrhage or intracranial aneurysms b. Seizure disorder unless seizure was >10 years ago, a single isolated event, no medications prescribed, and a normal neurological examination is documented c. Stroke or transient ischemic attack d. Immunologically mediated disease, celiac disease, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, sarcoidosis, severe psoriasis, or symptomatic thyroid disorder e. Chronic pulmonary disease f. Significant cardiac abnormalities/dysfunction including uncontrolled hypertension or use of antianginal agents g. Medical condition requiring chronic systemic corticosteroids h. Active gout i. Hemoglobinopathy, including thalassemia major j. Myelodysplastic syndromes k. Coagulopathy, including hemophilia l. Organ transplants other than cornea and hair m. Poor venous access precluding routine peripheral blood sampling n. Indwelling venous catheters o. Gastric surgery or malabsorption disorders 11. Malignancy within 5 years (except treated carcinoma in situ and basal cell carcinoma of the skin) 12. Pregnant or nursing or subjects who intend to become pregnant and male subjects with partners who are, or intend to become, pregnant 13. Condition unsuitable for enrollment 14. Life-threatening SAE screening 15. Not be a member or a family member of the sponsor staff directly involved with this trial. 16. Hematologic, biochemical, and serologic criteria: a. Hemoglobin <12 g/dL for females and <13 g/dL for males; b. Neutrophils <1500/mm3 (blacks/African-Americans: <1200/mm3); c. Platelets <100,000/mm3; d. Direct bilirubin >1.5 x upper limit of normal. Total bilirubin >1.6 mg/dL unless history of Gilbert's disease 17. Serum albumin below the lower limit of normal 18. Thyroid-stimulating hormone (TSH) >1.2 x ULN or <0.8 x LLN of laboratory range with the following exceptions: a. May be enrolled if clinically euthyroid b. Euthyroid function is confirmed by thyroxine/triiodothyronine (T4/T3) testing 19. Serum creatinine >ULN of the laboratory reference. 20. Serum glucose: a. No previous diagnosis with diabetes mellitus: i. ≥140 mg/dL (nonfasting) unless hemoglobin, A1c subtype (HbA1c) ≤7% ii. ≥100 mg/dL (fasting) unless HbA1c ≤7% b. Previously diagnosed with diabetes mellitus, HbA1c >8.5%. 21. Prothrombin time/partial thromboplastin time (PT/PTT) values >10% above range 22. Alpha fetoprotein (AFP): a. AFP >100 ng/mL b. AFP 50 to 100 ng/mL requires a liver ultrasound and subjects with findings suspicious for HCC are excluded. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the trial is the achievement of SVR, defined as undetectable plasma HCV-RNA at FW 24. If a subject is missing FW 24 data and has undetectable HCV-RNA at FW 12, the subject will be considered a sustained virologic responder. Subjects in any treatment arm will be declared treatment failures in one of the following ways: 1) Subjects with detectable HCV-RNA and a <2-log10 decline in HCV-RNA levels at TW 12. 2) Subjects with ≥LLQ HCV-RNA at TW 24. 3) Subjects with detectable HCV-RNA at FW 24. 4) Subjects who are missing their HCV-RNA at or after FW 24 and have detectable or missing HCV-RNA 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 | 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 | No |
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 | 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) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |