A Two-Part Study of Safety, Pharmacokinetics, and Efficacy of Telaprevir in Combination With Peginterferon alfa-2b and Ribavirin in Pediatric Subjects Infected With Hepatitis C Virus

• Conditions: genotype 1 Hepatitis C Virus; MedDRA version: 16.0Level: PTClassification code 10019744Term: Hepatitis CSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2011-004564-30-BE
• Lead Sponsor: Vertex Pharmaceuticals

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10-08
• Last Update Posted: 17 August 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 120
F.1.2 Adults (18-64 years) no
F.1.2.1 Numb

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified