A Phase III, randomized, double-blind, placebo-controlled study to investigate the efficacy, safety and tolerability of TMC435 vs. placebo as part of a treatment regimen including peginterferon alfa-2a and ribavirin in treatment-na?ve, genotype 1 hepatitis C-infected subjects - QUEST-1

• Register: EUCTR
• Last refreshed on: 1 April 2013
• Main ID: EUCTR2010-020444-36-IT
• Date of registration: 19/05/2011
• Prospective Registration: No
• Primary sponsor: TIBOTEC PHARMACEUTICALS LTD.
• Public title: A Phase III, randomized, double-blind, placebo-controlled study to investigate the efficacy, safety and tolerability of TMC435 vs. placebo as part of a treatment regimen including peginterferon alfa-2a and ribavirin in treatment-na?ve, genotype 1 hepatitis C-infected subjects - QUEST-1
• Scientific title: A Phase III, randomized, double-blind, placebo-controlled study to investigate the efficacy, safety and tolerability of TMC435 vs. placebo as part of a treatment regimen including peginterferon alfa-2a and ribavirin in treatment-na?ve, genotype 1 hepatitis C-infected subjects - QUEST-1
• Date of first enrolment: 15/03/2011
• Target sample size: 375
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020444-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Male or female subject aged = 18 years; liver biopsy within 3 years prior to the screening visit (or between the screening and baseline visit) with histology consistent with chronic HCV infection; subjects with bridging fibrosis (Metavir score F3) or cirrhosis (Metavir score F4) must have an ultrasound taken within 6 months prior to the screening visit (or between the screening and baseline visit) with no findings suspicious for hepatocellular carcinoma; genotype 1 HCV infection (confirmed at screening); plasma HCV RNA of > 10,000 IU/mL at screening; and no prior treatment with any approved or investigational drug for the treatment of hepatitis C.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Evidence of hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) 2. Any liver disease of non-HCV etiology. This includes acute hepatitis A, drug- or alcoholrelated liver disease, autoimmune hepatitis, hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the investigator. 3. Infection/co-infection with nongenotype 1 HCV. 4. Co-infection with HIV type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening). 5. Co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive). 6. Medical conditions which are contraindications for PegIFNa-2a or RBV therapy: a. Major uncontrolled depressive illness; b. Organ transplant (other than cornea or hair transplant or skin graft); c. Severe concurrent medical disease such as severe hypertension, significant coronary heart disease, poorly controlled diabetes, untreated thyroid disease, chronic obstructive pulmonary disease, severe infections (bacterial, viral, fungal, including acute tuberculosis), or hemoglobinopathies (thalassemia major or sickle-cell anemia); d. Autoimmune hepatitis or other autoimmune conditions known to be exacerbated by PegIFN and RBV. 7. Any other clinically significant disease that in the opinion of the investigator would be exacerbated by the known effects of PegIFN and RBV. 8. History of malignancy within 5 years of the screening visit (exceptions: squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

HAPATITIS C VIRUS IN TREATMENT NAIVE PATIENTS
MedDRA version: 13.1 Level: PT Classification code 10019744 Term: Hepatitis C System Organ Class: 10021881 - Infections and infestations
MedDRA version: 13.1 Level: LLT Classification code 10019183 Term: HCV System Organ Class: 10022891 - Investigations

Intervention(s)

Product Name: TMC435
Product Code: TMC435
Pharmaceutical Form: Capsule, hard
CAS Number: 923604-59-5
Current Sponsor code: TMC435
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective is: ? To demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including peginterferon alfa-2a (PegIFNa-2a) and ribavirin (RBV), with respect to the proportion of subjects with sustained virologic response (SVR) 24 weeks after the planned end of treatment (SVR24)

Primary end point(s): see section 11.2.1 of the protocol (page 72)

Secondary Objective: ? To demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including PegIFNa-2a and RBV, with respect to the proportion of subjects with SVR 12 weeks after the planned end of treatment (SVR12). ? To demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including PegIFNa-2a and RBV, with respect to the proportion of subjects with SVR at Week 72 (last study-related visit). ? To compare the antiviral activity of TMC435 versus placebo as part of a treatment regimen including PegIFNa- 2a and RBV at all time points, with focus on Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, and Week 72. ? To evaluate the incidence of viral breakthrough during the treatment period in the TMC435 and placebo treatment groups. ? To evaluate the relapse rate after treatment in the TMC435 and placebo treatment groups. ? To determine the viral NS3/4A sequence in subjects in the TMC435 treatment group with virologic failure.

Secondary ID(s)

TMC435-TiDP16-C208

2010-020444-36-GB