A Phase IIa, Double-blind, Randomised, Placebo-Controlled Dose Escalation Study to Evalulate the Safety, Tolerability, Pharmacokinetics and Activity of GS-9450, a Caspase Inhibitor, in Subjects with Chronic Hepatitis C

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2007-001601-16-NL
• Date of registration: 02/04/2007
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences Incorporated
• Public title: A Phase IIa, Double-blind, Randomised, Placebo-Controlled Dose Escalation Study to Evalulate the Safety, Tolerability, Pharmacokinetics and Activity of GS-9450, a Caspase Inhibitor, in Subjects with Chronic Hepatitis C
• Scientific title: A Phase IIa, Double-blind, Randomised, Placebo-Controlled Dose Escalation Study to Evalulate the Safety, Tolerability, Pharmacokinetics and Activity of GS-9450, a Caspase Inhibitor, in Subjects with Chronic Hepatitis C
• Date of first enrolment: 13/04/2007
• Target sample size: 32
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001601-16
• 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

France, Germany, Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
• Adult subjects, ages 18-65 infected with chronic HCV of any genotype who have previously been treated with RIBA and/or INF (or pegylated interferon) who either 1) did not achieve or maintain a sustained virologic response after RIBA and/or INF or 2) did not tolerate RIBA and/or INF treatment.
• Alternatively, subjects may be eligible if they have contraindications to receiving INF and/or RIBA therapy
• ALT = 1.5 x ULN but < 10 x ULN
• BMI between 19 and 32 kg/m2 (inclusive)
• Creatinine clearance = 70 mL/min
• absolute neutrophil count = 1000/mm3
• hemoglobin = 10 g/dL
• have no clinical or laboratory evidence of hepatic decompensation (i.e., subjects must have platelets = 75,000/mm3, total bilirubin = 1.5 x ULN, prothrombin time = 1.5 x ULN and albumin = 3.0 g/dL).
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) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• decompensated liver disease
• evidence of hepatocellular carcinoma (i.e., alpha-fetoprotein 50 ng/mL)
• positive urine drug screen for opiates, cocaine or amphetamines
• co-infection with hepatitis B virus (HBV)
• human immunodeficiency virus (HIV); pancreatitis
• recent significant infection or symptoms of infection (including mononucleosis or active herpes simplex virus)
• autoimmune disorders
• transplantation
• history of malignancy
• ongoing alcohol abuse (defined as intake of more than 28 units of alcohol per week


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

Health Condition(s) or Problem(s) studied

Chronic Hepatitis C
MedDRA version: 9.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C

Intervention(s)

Product Name: N/A
Product Code: GS-9450
Pharmaceutical Form: Capsule*
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5, 10, 40-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: • To investigate the safety and tolerability of multiple oral doses of GS-9450 in subjects with chronic hepatitis C (HCV).

Secondary Objective: • To investigate the pharmacokinetics of multiple oral doses of GS 9450 and its metabolites in subjects with chronic HCV

• To investigate the activity of multiple oral doses of GS 9450 in subjects with chronic HCV, as evidenced by: (1) change from baseline in alanine aminotransferase (ALT) levels (primary activity measure), (2) change in aspartate aminotransferase (AST) levels, and (3) change in noninvasive markers indicative of hepatic apoptosis, including cytokeratin 18 caspase-cleavage fragment [CK-18])

• To investigate the effects of GS 9450 on hepatitis C viral load

Primary end point(s): • The primary safety endpoint will evaluate the tolerability of multiple oral doses of GS-9450. This endpoint will be assessed as treatment limiting adverse events or laboratory abnormalities that require premature discontinuation from the study.

• The primary activity endpoint will be change from baseline in ALT levels at Day 14.

• The primary pharmacokinetic endpoints of this study are to characterize the plasma PK parameters of GS-9450 and metabolites following multiple doses of GS-9450 using standard non compartmental methods.

Secondary ID(s)

GS-US-227-0102