| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| chronic genotype 1 hepatitis C infection |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | LLT |
| E.1.2 | Classification code | 10008912 |
| E.1.2 | Term | Chronic 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 |
- to provide access to telaprevir for subjects with chronic HCV genotype 1 infection who were randomized to the control group in the C216 trial and who failed therapy for virologic reasons;
- to evaluate efficacy, safety, and tolerability of telaprevir in combination with
Peg-IFN alfa-2a and RBV in these subjects;
- to evaluate amino acid changes from baseline in the HCV NS3 protease domain. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject was randomized to the control group in the C216 trial and failed therapy for virologic reasons.
The investigator will receive an invitation sent by the unblinded independent virology
monitor of the C216 trial for those subjects of the C216 trial who were randomized to the control group and who failed therapy for virologic reasons. This invitation should be kept in the subject’s file.
2. Before entry in the current trial, all assessments in the C216 trial, including the Safety Follow-up Visit, will have to be completed.
3. Subject is judged to be in good health (besides HCV infection) in the opinion of the
investigator, on the basis of medical history, physical examination, screening vital signs, screening electrocardiogram [ECG], and screening laboratory tests, with any chronic medical conditions under stable medical control.
4. If heterosexually active, a female subject of childbearing potential and a non-vasectomized male subject who has a female partner of childbearing potential must agree to the use of 2 effective methods of contraception from screening onwards until 6 months (female subject) or 7 months (male subject) after the last dose of RBV (see also Section 5.2.4).
Note: Male subjects should use a male condom. This birth control method should be
combined with another effective method such as hormonal contraceptives (like the patch, or the pill), intrauterine device, diaphragm with spermicidal jelly or cervical cap.
Note: Hormonal contraceptives may not be reliable when taking telaprevir. Therefore, to be eligible for this trial, subjects should use 2 other effective birth control methods during telaprevir treatment and for 2 months after the last intake of telaprevir. As of 2 months after completion of telaprevir treatment, hormonal contraceptives can again be used as one of the 2 required effective methods of birth control.
Note: The use of birth control methods does not apply if the male partners have been
vasectomized minimally 1 month prior to screening or if the female partners have had a bilateral oophorectomy, a total hysterectomy, or tubal ligation, or if they have been
post-menopausal for at least 2 years.
5. Subject is willing and able to refrain from the concomitant use of any medications,
substances, or foods noted under the Section 5.3.11, from 14 days prior to the first day of study medication dosing through the end of treatment.
6. Subject is able to read and understand, and is willing to sign the ICF voluntarily before first trial-related activity and abide by the trial restrictions.
7. Subjects should agree not to participate in other clinical trials for the duration of his/her participation in this trial, except for non-interventional or observational trials and after prior approval of the sponsor.
|
|
| E.4 | Principal exclusion criteria |
1. Subjects who prematurely discontinued study medication in the C216 trial because of noncompliance (as deemed by the investigator) or for whom repeated treatment would be inappropriate for safety reasons.
2. Subject received any direct acting anti-viral HCV therapy after discontinuation of the C216 trial.
3. Subject has developed any new contraindication to the administration of Peg-IFN alfa-2a or RBV since his/her enrollment in the C216 trial, including but not limited to any of the following:
- hypersensitivity to Peg-IFN alfa-2a, RBV, or any of their components;
- newly acquired hemoglobinopathies;
- history or clinical evidence of significant or unstable cardiac disease (e.g. angina,
congestive heart failure, recent myocardial infarction, significant arrhythmia) and/or
clinically significant ECG abnormalities;
- abnormal thyroid function that is not controlled effectively by medication;
- eye abnormalities at the recommended pretreatment opthalmological clearance;
- creatinine clearance <=50 mL/min at screening;
- evidence of autoimmune condition.
4. Subject has an active of pre-existing psychiatric condition that in the opinion of the
investigator could interfere with the subject’s participation in and completion of the trial for safety and for other reasons.
5. Subject has history of decompensated liver disease: history of ascites, hepatic
encephalopathy, or bleeding esophageal varices, and/or any of the following screening laboratory results:
- International Normalized Ratio (INR) of >=1.5;
- Serum albumin < 3.3 g/dL;
- Serum total bilirubin > 1.8 times upper limit of laboratory normal range (ULN), unless isolated or in subjects with Gilbert’s Syndrome.
6. Subject has active malignant disease or history of malignant disease within the past 5 years (with the exception of treated basal cell carcinoma).
7. Subject with cirrhosis who has hepatocellular carcinoma. For subjects with cirrhosis, AFP level will be measured and an abdominal ultrasound will be performed in order to screen for hepatocellular carcinoma. In case of AFP > 50 ng/mL or ultrasound being abnormal, subjects must also have a CT or MRI scan to exclude hepatocellular carcinoma. Assessments of the AFP level and ultrasounds (and CT or MRI scans if necessary) will be performed at screening, unless these assessments have been performed in the C216 trial within 6 months prior to screening in the current trial.
8. Subject has history of seizure disorders.
9. Subject has history of organ transplant that requires chronic immunosuppression (Note: corneal, skin, and hair grafts are allowed).
10. Subject has a medical condition that requires use of systemic corticosteroids
11. Diabetic or hypertensive subject with clinically significant ocular exam findings, e.g., retinopathy, cotton wool spots, and optic nerve disorder. Clearance by an ophthalmologist is required within 3 months prior to screening or within the screening period. The ophthalmologist should conduct a fundoscopic exam, which should be documented in the subjects’ records. The findings of the exam must also be recorded on the eCRF.
12. Subject has evidence of serious or severe bacterial or fungal infection(s), including active tuberculosis.
13. Subject has HIV or hepatitis B virus (HBV) co-infection.
14. Subject has a history of acute or chronic pancreatitis.
15. Suspicion exists of alcohol, barbiturate, or amphetamine recreational or narcotic drug use, current or within 2 years prior to the screening visit, that in the investigator’s opinion would compromise the subject’s safety and/or compliance with study procedures.
16. Subject or female partner is pregnant or planning to become pregnant.
17. Subject is breastfeeding.
18. Subject has any clinically significant laboratory abnormalities as judged by the investigator, with the following exceptions:
- Grade 3 elevations in transaminsases ([ALT], [AST]). However, ALT/AST levels at screening should not exceed 10 times ULN.
- Grade 3 elevations in GGT. However, subjects with grade 3 GGT elevations will only be allowed to enter the trial if there is no evidence of current alcohol abuse and if the GGT elevations are not associated with other clinically relevant laboratory abnormalities, as judged by the investigator.
OR
Subject has screening laboratory values of the following variables that do not meet the acceptable values defined below:
Absolute neutrophil count ≥ 1,200/mm3, Platelet count ≥ 90,000/mm3, Hemoglobin ≥ 12 g/dL for females ≥ 13 g/dL for males, Thyroid-stimulating hormone (TSH) Within normal range, or adequately controlled thyroid function on treatment
19. Subject has congenital or acquired prolonged QT interval, or a history of nonsustained or sustained ventricular tachycardia, or history of drug-induced QT prolongation and/or Torsade de Pointes that in the investigator’s opinion would compromise the subject’s safety. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| plasma HIV RNA quantification |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| 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 | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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 | No |
| E.8.1.1 | Randomised | No |
| 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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| roll-over of VX-950-TiDP24-C216 |
|
| 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 | 1 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 44 |
| 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 |
| Austria |
| Belgium |
| Canada |
| France |
| Germany |
| Italy |
| Netherlands |
| Poland |
| Spain |
| Sweden |
| Switzerland |
| United Kingdom |
|
| 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 | 5 |
| E.8.9.1 | In the Member State concerned days | 14 |
| 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 | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 14 |
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