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 | 13.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021881 |
E.1.2 | Term | Infections and infestations |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10019805 |
E.1.2 | Term | Hepatobiliary disorders |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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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 study is to compare the efficacy of boceprevir (PO) in combination with peginterferon alfa-2b (PEG2b) (SC) plus ribavirin weight-based dosing (WBD) PO to therapy with PEG2b plus ribavirin alone in adult subjects coinfected with human immunodeficiency virus (HIV) and previously untreated chronic hepatitis C virius (HCV) genotype 1. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety of boceprevir when used in combination with PEG2b/R - To define predictors of SVR such as epidemiologic factors, disease characteristics and on-treatment response - To assess the steady state pharmacokinetics of boceprevir using population-based pharmacokinetic modeling
"Key Secondary Trial Objective: The key secondary objective of this trial is to compare the efficacy of boceprevir when used in combination with PEG2b + R (WBD) to the standard of care (PEG2b + R) alone in randomized subjects who received at least one dose of experimental trial medication (Placebo for the control arm and boceprevir for the experimental arm)." |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The subject must fulfill ALL the criteria listed below for entry: 1. Each subject must be willing and able to provide written informed consent 2. Subject must be ≥18 and ≤65 years of age 3. Subject must have a body weight ≥40 and ≤125 kg 4. Subject must have a documented history of HIV infection for greater than 6 months prior to Day 1 5. Subject must be on an optimized anti-retroviral treatment regimen (OTR) with stable HIV disease with CD4 ≥200 cells/mcL and HIV-1 RNA viral load <50 copies/mL 6. Subject must have documented CHC genotype 1 infection (HCV infection greater than 6 months prior to Day 1). Subjects with other or mixed genotypes are not eligible. The HCV-RNA result obtained at the Screening Visit must confirm genotype 1 infection and be ≥10,000 IU/mL 7. 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 trial site must be able to access the pathology report and histology slides prior to subject randomization. Two unstained slides are preferred; however, one slide stained with hematoxylin plus eosin (H and 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’s reading will be used for analysis purposes only; randomization will be performed based on the local report a. If no cirrhosis is present: The liver biopsy must be within 2 years of the Screening Visit b. If cirrhosis is present: Any historic liver biopsy demonstrating cirrhosis will be accepted regardless of the length of time since biopsy. Refer to Appendix 1 for the Scoring Systems for Hepatic Fibrosis c. If the timing of the liver biopsy does not meet the criteria outlined in Inclusion Criteria Nos. 7a and 7b, a 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) 8. Subject with bridging fibrosis or cirrhosis 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) 9. Subject and subject’s heterosexual partner(s) must each agree to use acceptable methods of contraception for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of trial medication, or longer if dictated by local regulations |
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E.4 | Principal exclusion criteria |
Clinical Exclusion Criteria: 1. Prior HCV treatment except herbal remedies must be discontinued except silymarin 2. Coinfected w/ hepatitis B virus or signs/symptoms of infection 3. Decompensated liver disease: ascites, bleeding varices, or hepatic encephalopathy 4. Anti-retroviral regimen change w/in 3 months (except zidovudine, didanosine, stavudine) efavirenz, etravirine, nevirapine & HIV protease inhibitors w/out ritonavir 5. Use of zidovudine, didanosine, stavudine, efavirenz, etravirine, nevirapine w/in 1 month & during the trial 6. Significant opportunistic infections w/in 1yr 7. Diabetic & hypertensive subjects w/ocular findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any abnormality 8. Pre-existing psychiatric condition: a. Moderate or severe depression b. Depression associated with: 1) Hospitalization 2) Electroconvulsive Therapy 3) Prolonged work absence or disruption of daily functions c. Suicidal or homicidal ideation/attempt d. Severe psychiatric disorders e. Lithium use f. Antipsychotic drug 9. Substance abuse: alcohol, intravenous drugs, inhalational (not marijuana), psychotropics, narcotics, cocaine, prescription or OTC drugs or history of polysubstance abuse (≥3) 10. Clinical diagnosis w/in 6 months of substance abuse Clinical diagnosis requires: a. Documentation w/in 6 months of a low risk for psychiatric exacerbation induced by interferon b. Documentation of compliance by an HIV viral load <400 copies/mL for ≥ 1yr 11. Receiving opiate agonist substitution therapy but not in a substitution maintenance program 12. Marijuana deemed excessive or interfering w/subject's life. Stop use of recreational marijuana prior to trial 13. Pre-existing medical condition interfering with participation a. Central nervous system trauma requiring intubation, intracranial pressure monitoring, brain meningeal or skull surgery, or resulting in seizure, coma, permanent neurologic deficits, abnormal brain imaging, cerebrospinal fluid leak, or prior brain hemorrhage and/or intracranial aneurysms b. Seizure disorder unless seizure was >10 years ago, an isolated event, no anti-seizure medications prescribed, & a normal neurological examination documented w/in 6 months c. Stroke or transient ischemic attack d. Immunologically-mediated disease e. Chronic pulmonary disease f. Significant cardiac abnormalities/dysfunctions including uncontrolled hypertension, or history of antianginal agents for cardiac conditions g. Conditions requiring, or likely to require, chronic systemic administration of corticosteroids h. Active clinical gout w/in 1 year i. Hemoglobinopathy j. Myelodysplastic syndromes k. Coagulopathy l. Organ transplants other than cornea & hair m. Poor venous access precluding routine blood sampling n. Indwelling venous catheters o. Gastric surgery or malabsorption disorders 14. Malignancy w/in the last 5yrs 15. Subjects pregnant or nursing, who intend to become pregnant, & male subjects w/partners who are, or intend to become pregnant 16. Other conditions unsuitable for enrollment or could interfere w/participating 17. Intent to or participation in other clinical trials w/in 30 days of randomization. Collection of blood, urine, or tissue samples or data, beyond this protocol, is prohibited 18. Treatment w/an investigational drug w/in 30 days of randomization 19. Site personnel involved w/the trial 20. Family members of the trial staff 21. Life-threatening serious adverse event during screening 22. Subjects with HIV-2 23. Use of any HIV protease inhibitor w/out the coadministration of ritonavir w/in 1 month and during the trial Laboratory Exclusion Criteria: 1. Hematologic, biochemical, & serologic criteria: a. Hemoglobin <11 g/dL, females & <12 g/dL, males b. Neutrophils <1500/mm^3 (blacks/African-Americans: <1200/mm^3) c. Platelets <100,000/mm^3 d. Direct bilirubin >1.5 x ULN (upper limit of normal) of the reference range. Total bilirubin >1.6 mg/dL unless Gilbert's disease or regimen contains atazanavir 2. Serum albumin <LLN (lower limit of normal) of reference range 3. Thyroid-stimulating hormone >1.2 x ULN or <0.8 x LLN of reference range with the following exceptions a. Enrolled if clinically euthyroid, AND b. Euthyroid function confirmed by T3/T4 test 4. Serum creatinine >ULN of the reference range 5. Serum glucose a. Not previously diagnosed with diabetes mellitus i. ≥140 mg/dL (non-fasting) unless HbA1c ≤7% OR ii. ≥100 mg/dL (fasting) unless HbA1c ≤7% b. Diabetes mellitus, HbA1c >8.5% 6. Prothrombin time/ Partial thromboplastin time values >10% above reference range 7. Alpha fetoprotein: a. AFP >100 ng/mL OR b. AFP 50 to 100ng/mL 24. Receiving any of the following medications w/in 2 weeks: alfuzosin, antiarrhythmics (amiodarone, bepridil, flecainide,propafenone, & quinidine), ergot derivatives, cisapride, lovastatin, simvastatin, pimozide, triazolam, and orally administered midazolam |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint for the trial is: the achievement of SVR, defined as undetectable plasma HCV-RNA at follow-up week (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 will be declared treatment failures in one of the following ways: - Subjects in any treatment arm who have detectable HCV-RNA at FW 24 - Subjects in any treatment arm with a <2 log10 decline in HCV-RNA at TW 12 - Subjects in any treatment arm with ≥LLQ HCV-RNA at TW 24 - Subjects in any treatment arm 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 | 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 | 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 | 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 | Yes |
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 | Yes |
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 | 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 | 18 |
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |