E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
genotype 1 Hepatitis C Virus |
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E.1.1.1 | Medical condition in easily understood language |
genotype 1 Hepatitis C Virus |
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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 | 16.0 |
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 |
PART A
- To evaluate the short-term safety of telaprevir in combination with peginterferon alfa-2b (Peg-IFN) and ribavirin (RBV) (Peg-IFN/RBV) in treatment-naïve pediatric subjects without cirrhosis
- To evaluate the pharmacokinetics (PK) and determine the appropriate dose of telaprevir in combination with Peg-IFN/RBV in treatment-naive pediatric subjects without cirrhosis
PART B
- To evaluate the safety of telaprevir in combination with Peg-IFN/RBV in treatment-naive and peginterferon/RBV treatment-experienced pediatric subjects with or without cirrhosis |
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E.2.2 | Secondary objectives of the trial |
PART A
- To evaluate the efficacy of telaprevir in combination with Peg-IFN/RBV in treatment-naive pediatric subjects without cirrhosis
PART B
- To evaluate the efficacy of telaprevir in combination with Peg-IFN/RBV in treatment-naive and peginterferon/RBV treatment-experienced pediatric subjects with or without cirrhosis
- To evaluate the PK of telaprevir in combination with Peg-IFN/RBV in treatment-naive and peginterferon/RBV treatment-experienced pediatric subjects with or without cirrhosis |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females ages 3 to 17 years of age, inclusive, on the date of signed informed consent form (ICF), and where appropriate, date of assent
2. Chronic hepatitis C based on serum antibody or HCV RNA detectable at least twice, at least 6 months apart; measurable HCV RNA in the blood; and evidence of liver inflammation documented by abnormal liver transaminases or by a liver biopsy
a. If a liver biopsy is available, it must have been performed within 2 years of screening
b. Treatment can be initiated if histopathology shows fibrosis >Stage 0 or inflammation >Grade 0
c. An elevation of ALT within 1 year of screening
3. Hepatitis C virus RNA ≥1000 IU/mL at the Screening Visit
4. Hepatitis C virus genotype 1a or b at the Screening Visit
5. One of the following:
a. Hepatitis C virus treatment-naive subjects may not have received any previous treatment, experimental or approved, for hepatitis C (Part A and Part B).
b. Peginterferon/RBV prior relapse (Documented undetectable HCV RNA level at the planned EOT of at least 42-week duration [HCV RNA evaluated within 6 weeks after the last dose of medication] but did not achieve SVR24. Start and stop dates of
treatment must be documented. The last dose of peginterferon/RBV must have been at least 12 weeks before the Screening Visit.) (Part B only).
c. Peginterferon/RBV prior null responder (Part B only):
- Failure to decrease HCV RNA by <2 logs after at least 12 weeks of therapy. For documentation of prior treatment experience Week 12 response, a Week 11 to 24 window is allowed.
d. Peginterferon/RBV prior partial responder (Part B only):
- Had a ≥2 log decrease in HCV RNA at Week 12 but never achieved undetectable HCV RNA while on treatment (partial responder). For documentation of prior treatment experience Week 12 response, a Week 11 to 24 window is allowed. Subjects must have received the last dose of peginterferon/RBV at least 12 weeks before the Screening Visit.
The following information related to the virologic response to the last course of peginterferon/RBV must be available in the medical records of the subject:
- Start and end date of the previous treatment course
- Hepatitis C virus RNA results before the start of treatment (all subjects), after at least 12 weeks of treatment (null and partial responders), at EOT (all subjects), and during follow-up (relapsers). The most recent HCV RNA value obtained within 6 months before the start of prior treatment is to be used as the baseline.
6. Subject is judged to be in good health (besides HCV infection) in the opinion of the investigator, on the basis of medical history and physical examination (including vital signs and screening ECG), with any chronic medical conditions under stable medical control
7. Female subjects of childbearing potential must agree to either remain abstinent or to use 2 effective methods of contraception from at least 14 days before first dose of study drug through 6 months after the last dose of RBV. Male subjects who have a female partner of childbearing potential must agree to either remain abstinent or to use 2 effective methods of contraception from Day 1 through 7 months after the last dose of RBV.
8. Signed ICF, and where appropriate, signed Assent Form
9. Able to refrain from concomitant use of any medications, substances, or foods as described in the Study Protocol. |
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E.4 | Principal exclusion criteria |
1. History of or prior evidence of a medical condition associated with chronic liver disease other than HCV, including, but not limited to, hepatitis B, abnormal ceruloplasmin, alpha-1-antitrypsin, ANA >1:640, smooth muscle antibody >1:80, anti-liver/kidney microsomal antibody >60 units, hepatic malignancy or malignancy with prior hepatic involvement, drug- or alcohol-related hepatitis or cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson’s disease, and clinically significant steatosis
2. Body weight <15 kg or >90 kg
3. Prior evidence of hepatic decompensation: history of ascites, hepatic encephalopathy, or bleeding esophageal varices and/or laboratory results as indicated in the Study Protocol
4. Clinical suspicion in the opinion of the investigator for pubertal growth spurt and risk for growth delay that may outweigh the benefit of HCV treatment, to be assessed on a case by case basis as described in the Peg-IFN EU SmPC
5. Serum alfa-fetoprotein (AFP) ≥10 ng/mL at the Screening Visit or clinical suspicion of hepatocellular carcinoma.
6. Positive test at the Screening Visit for HBV DNA, anti-HAV immunoglobulin M antibody, or anti-HIV antibody
7. Screening laboratory values as listed in the Study Protocol
8. Contraindications to Peg-IFN/RBV
9. History of congenital QT prolongation or family history of congenital QT prolongation or sudden death
10. History of autoimmune or immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis)
11. Active malignant disease or history of malignant disease (except for subjects in complete remission for >5 years from leukemia)
12. History of a chronic medical condition that in the opinion of the investigator may preclude study participation
13. Major depression according to the CDI 2TM or a history of severe psychiatric disorder, such as major psychoses, severe anxiety or personality disorder, suicidal ideation and/or suicide attempt, or any psychiatric condition that in the opinion of the investigator would preclude study participation (Subjects newly identified to have major depression by the CDI 2TM should be referred to a mental health clinic or specialist.)
14. History or other evidence of chronic pulmonary or cardiac disease associated with functional limitation
15. History of craniocerebral trauma that in the opinion of the investigator could lead to a lower threshold for seizure or active seizure disorder requiring medication
16. History of organ transplant (except cornea or skin)
17. Medical condition that requires frequent or prolonged use of systemic corticosteroids (e.g., severe asthma or autoimmune conditions)
18. History or other evidence of severe retinopathy or clinically significant ophthalmological disorder including, but not limited to, disease due to diabetes mellitus or hypertension. For subjects with a history of hypertension or diabetes, fundoscopic examination within the Screening Period by a physician or documented within 60 days of Day 1 is required to exclude baseline retinopathy.
19. History of intercurrent illness (e.g., upper respiratory illness with fever) within 5 days before the first dose of study drug
20. History of non-genotype 1 HCV
21. Currently using drugs (illicit drugs or controlled narcotics) or alcohol. A urine screen positive for drugs of abuse as described in the Study Protocol except for subjects with positive drug screen for opiates, cannabinoids, benzodiazepines, or tricyclic antidepressants for which the investigator deems these not be to drugs of abuse.
22. History of recent drug or alcohol abuse that would, in the opinion of the investigator, limit adherence or compliance to the study
23. Participation in
a. any investigational drug study within 90 days before Day 1
b. more than 2 investigational drug studies in the 12 months before Day 1
c. any concurrent research study from screening until the end of the subject’s participation in this study including observational studies, which involve treatment, blood draws, or intervention. Participation in observational studies without treatment, blood draws, or intervention is allowed.
d. an investigational drug study in which it is unknown whether the subject was treated with an HCV protease inhibitor
24. Any condition likely to affect gastrointestinal tract absorption (e.g., gastrectomy)
25. Any disease of iron overload, including hemochromatosis, and diseases requiring repeat transfusions
26. Use of prohibited drugs (as described in the Investigator’s Brochure and contraindicated in package inserts for telaprevir, Peg-IFN, and RBV) within 7 days or 5 half-lives (whichever is longer) before the first dose of study drug
Additional exclusion criteria apply only to Part A:
27. Previously documented cirrhosis
28. Previously treated for hepatitis C with any approved or experimental treatment |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety parameters, including AEs, study drug modifications or discontinuations, clinical laboratory values, vital signs, and electrocardiogram (ECG) assessments |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Proportion of subjects who achieve undetectable HCV RNA 12 weeks after the last planned dose of study drug (SVR12)
- Proportion of subjects who achieve undetectable HCV RNA 24 weeks after the last planned dose of study drug (SVR24)
- Proportion of subjects who achieve undetectable HCV RNA at Week 4, at Week 12, at both Weeks 4 and 12 (eRVR), and at the planned end of treatment (EOT)
- Proportion of subjects with on-treatment virologic failure, defined as either meeting a futility rule or completing the assigned treatment duration with detectable HCV RNA at the EOT
- Proportion of subjects with virological relapse, defined as having undetectable HCV RNA at planned EOT followed by detectable HCV RNA after planned EOT
- Part A only: PK of telaprevir (including maximum observed plasma concentration [Cmax], time to maximum plasma concentration [tmax], area under the plasma concentration versus time curve [AUC], and elimination half-life [t1/2])
- Changes from baseline in the amino acid sequence of the HCV NS3•4A protease |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 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 | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Belgium |
France |
Germany |
Italy |
Spain |
United Kingdom |
United States |
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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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Last Patient 5 Years (±1 month) extended follow-up visit after last dose of study drugs |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |