chronic hepatitis C MedDRA version: 20.0 Level: SOC Classification code 10019805 Term: Hepatobiliary disorders System Organ Class: 10019805 - Hepatobiliary disorders MedDRA version: 20.0 Level: SOC Classification code 10021881 Term: Infections and infestations System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: ZEPATIER - 50 MG/100 MG- COMPRESSA RIVESTITA CON FILM- USO ORALE- BLISTER (ALL/ALL)- 28 COMPRESSE
Product Name: Zepatier
Pharmaceutical Form: Tablet
INN or Proposed INN: grazoprevir
CAS Nu
Sponsors
AZIENDA OSPEDALIERA UNIVERSITARIA POLICLINICO “PAOLO GIACCONE” DI PALERMO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Willing and able to provide written informed consent • Male or female, age = 18 years • Chronic HCV infection (= 6 months) documented by prior medical history or liver biopsy, only genotype 1b virus. (Positive for anti HCV antibody, HCV RNA, or an HCV genotype) • Treatment-naïve with no prior exposure to any IFN, RBV, or approved or experimental HCV-specific DAA • Non severe fibrosis (F= 2) according to Metavir score if a biopsy was performed or elasticity measured by Fibroscan® lower than 9.5 kPa or Fibrotest® lower than 0.59 or Fibrometer® lower than 0.63 if Fibroscan® cannot be performed. • Patients who are HBV core antibody positive. These patients should be monitored for hepatitis flare or HBV reactivation during HCV treatment and post treatment follow-up. Appropriate patient management for HBV infection as clinically indicated should be initiated as recommended by the European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol (2017). • Females of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 prior to enrollment • Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use 2 effective method(s) of contraception from at least two weeks prior to Day 1 through 14 days after the last dose of study drugs. • A female subject who is not of reproductive potential is eligible without requiring the use of contraception. A female subjects who is not of reproductive potentials is defined as one who has either 1) reached natural menopause (defined as 12 months with no menses without an alternative medical cause), 2) 6 weeks post surgical bilateral oophorectomy with or without hysterectomy, or 3) bilateral tubal ligation. • A male subject who is not of reproductive potential is eligible without requiring the use of contraception. A male subject who is not of reproductive potential is defined as: one who has undergone a successful vasectomy. A successful vasectomy is defined as: (1) microscopic documentation of azoospermia, or (2) a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post vasectomy. • Lactating females must agree to discontinue nursing before starting study drug • Subject must be of generally good health, with the exception of chronic HCV infection, and glucose abnormalities as determined by the Investigator • Subject must be able to comply with the dosing instructions for study drug administration 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 55 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: • Is under the age of legal consent, is mentally or legally incapacitated, has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, would interfere with the study procedures. • Current or prior history of any of the following: o Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded o Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug o History of decompensation (e.g., clinical ascites, encephalopathy, and/or variceal hemorrhage) o Solid organ transplantation (including hematopoietic stem cell transplants) other than kidney, cornea and hair. o Significant cardiac disease o Unstable psychiatric condition including hospitalization, suicidal attempt, and/or a period of disability as a result of their psychiatric illness within 2 years prior to Screening o Malignancy within the 5 years prior to Screening, with the exception of specific cancers that have been cured by surgical resection (e.g., basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are not eligible o Significant drug allergy (e.g., hepatotoxicity) • Subject has the following laboratory parameters at Screening: o ALT > 10 x the upper limit of normal (ULN) o AST > 10 x ULN o Direct bilirubin > 1.5 x ULN o Platelets 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regime affecting INR • Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency, cholangitis) • Infection with human immunodeficiency virus (HIV) • HBsAg positive patients • Clinically-relevant alcohol or drug abuse within 12 months of Screening. • Use of any prohibited concomitant medication listed in the specific SmPC section. • Known hypersensitivity to the study drug, the metabolites, or formulation excipient • Is currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another study. • (female) is pregnant, lactating, expecting to conceive or donate eggs, or is of childbearing potential and unwilling to commit to two methods of birth control throughout treatment and after the completion of all treatment (see Inclusion Criteria); or male subject is planning to impregnate or provide sperm donation or has a female sexual partner of childbearing potential and is unwilling to commit to using a two methods of birth control throughout treatment and after the completion of all treatment (see Inclusion Criteria). • had a life-threatening SAE during the screening period. • is a member or a family member of the investigational study staff or sponsor staff directly involved with this study. • has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis. • For subjects diagnosed with diabetes mellitus, documented HbA1c >8.5% (to exclude uncontrolled diabetes) • Has any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the proportion of subjects with sustained viral response 12 (SVR 12) weeks after cessation of treatment in HCV-Infected Patients, with non- severe fibrosis, with or without insulin resistance (IR) and/or diabetes mellitus (DM) treated with EBR/GZR Fixed-Dose Combination for 8 Weeks in G1b Treatment-Na¿ve. .;Secondary Objective: To evaluate the safety/tolerability of EBR/GZR treatment To determine the proportion of subjects who attain SVR at 24 weeks after cessation of treatment (SVR24) To evaluate the proportion of subjects with virologic failure To evaluate the emergence of viral resistance to EBR/GZR at failure To evaluate insulin resistance using homeostatic model assessment of insulin resistance (HOMA-IR) at baseline and follow-up week 12 (exploratory analysis) Comparisons between clinically relevant subgroups (including IR and DM) according SVR12 and SVR24 (exploratory analysis ;Primary end point(s): • To evaluate the proportion of subjects with SVR 12 weeks after cessation of treatment in HCV-Infected Patients, with non- severe fibrosis, with or without IR and/or DM treated with EBR/GZR Fixed-Dose Combination for 8 Weeks in G1b Treatment-Naïve [Time Frame: at 12 weeks ];Timepoint(s) of evaluation of this end point: 20 weeks from start of therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ¿ Evaluation of the safety and tolerability of EBV/GZR treatment by number of patients with treatment-related adverse events reported [Time Frame: 12 weeks after cessation of treatment ] ¿ Proportion of subjects who attain SVR24 [Time Frame: at 24 weeks after cessation of treatment ] ¿ Proportion of subjects with virologic failure [Time Frame: until 12 weeks after cessation of treatment ] ¿ Evaluation of the emergence of viral resistance to EBV/GZR during treatment and until 12 weeks after cessation of treatment in failing patients [Time Frame: until 12 weeks after cessation of treatment ] ¿ Assessments of insulin resistance were measured using HOMA-IR at baseline and follow-up week (FW)12 (exploratory analysis) ¿ Comparisons between clinically relevant subgroups (including IR and DM) according SVR12 and SVR24 (exploratory analysis) ;Timepoint(s) of evaluation of this end point: 24 weeks from start of therapy | — |
Countries
Italy
Contacts
Public ContactBioetica
Azienda Policlinico di Palermo
Outcome results
None listed