Chronic HCV associated with chronic arthritis. MedDRA version: 21.0 Level: LLT Classification code 10066550 Term: Chronic arthritis System Organ Class: 100000004859 MedDRA version: 20.1 Level: PT Classification code 10008912 Term: Chronic hepatitis C System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: HARVONI - 90 MG/400 MG - COMPRESSE RIVESTITE CON FILM - USO ORALE - FLACONE (HDPE) - 28 COMPRESSE RIVESTITE CON FILM
Product Name: HARVONI
Product Code: J05AX65
Pharmaceutical Form: Film-
Sponsors
AOU DI BOLOGNA POLICLINICO S.ORSOLA-MALPIGHI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Males or females, age > 18 years old • HCV treatment-naïve or INF-experinced without directly acting antiviral drugs, - Non-responder: The patient who had less than 2 log reduction of HCV-RNA after 12 weeks of antiviral treatment with IFN based regimen. - Partial responder: Patient with reduction =2 log ofHCV-RNA after 12 weeks of antiviral treatment with IFN based regimen. With persistence of positivity of HCV-RNA - Relapser: patient with undeceteable HCV-RNA at the end of antiviral treatment with IFN based regimen but with relapse (HCV-RNA positive) after discontinuation of treatment. • Chronic HCV infection documented by: a positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit, or a liver biopsy performed prior to the Baseline/Day 1 visit with evidence of chronic HCV infection HCV RNA = 104 IU/mL at Screening • Cirrhosis determination: i) Liver biopsy showing cirrhosis (e.g. Metavir score = 4 or Ishak score = 5) ii) FibroScan > 12.5 kPa • Liver imaging within 6 months of Baseline/Day 1 to exclude hepatocellular carcinoma is required in patients with cirrhosis • Radiological and laboratory diagnosis of inflammatory rheumatoid arthritis both seropositive (rheumatoid) and seronegative. serological positive and negative (RF+/-, anti-CCP +/-, cryo +/-) • HCV genotype 1 at Screening. • Screening ECG without clinically significant abnormalities • Laboratory tests documenting ALT=10 the upper limit of normal (ULN), Direct bilirubin = 1.5 × ULN; Platelets= 50,000 • Hemoglobin = 10 g/dL for female, = 11 g/dL for male subjects. • Albumin = 3g/dL • INR = 1.5 x ULN • Subject has not been treated with any investigational drug or device within 30 days of the Screening visit • Contraception - Female subjects (or the partner of a male subject) of childbearing potential must use effective contraception =1 method (=1% failure rate) during the study and up to seven months after discontinuation of RBV. - Male subjects with female partners of childbearing potential must use adequate contraception during treatment with ribavirin and for 7 months after the end of treatment - The effective contraception methods are those listed below: ¿ A double barrier method, (a) condom (male or female) or (b) diaphragm with spermicide; ¿ Intrauterine device; ¿ Vasectomy (partners); ¿ Hormonal (eg, contraceptive pill, patch, intramuscular injection or implant); ¿ Abstinence, abstinence is defined as abstaining from heterosexual relationships throughout the duration of therapy and up to seven months after discontinuation). 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Patients unable to receive oral therapy • Patients unable to give written informed consent • Subjects with clinically-significant illness (other than HCV and seronegative arthritis) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol • Pregnant or nursing female or male with pregnant female partner. • Severe hepatic impairment (Child-Pugh Classification B or C) or decompensated liver cirrhosis • Active malignancy or previous malignancy in the last five years • Solid organ transplantation HBV or HIV coinfection (HBsAg and/or anti-HIV positive). • Creatinine clearance < 30 mL /min (Cockcroft-Gault) • Active use of Sofosbuvir or ledipasvir prohibited medications • Any prior exposure to an HCV nonstructural protein (NS)5a-specific inhibitor or any direct acting antiviral drug. • Contraindications to treatment with RBV: - A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six months - Patients with chronic renal failure and / or on hemodialysis. - Haemoglobinopathies (eg thalassemia, sickle cell anemia • Administration of any prohibited drug within 28 days preceding the Baseline / Day 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.Evaluate the efficacy of SOF/LDV¿RBV in achieving arthritis remission/improvement, at end of the antiviral treatment in patients with CHC genotype 1 (na¿ve and experienced) both with and without cirrhosis CHILD-A with both seropositive and seronegative arthritis.;Secondary Objective: 1.Evaluate the safety of the combination SOF/LDV¿RBV for 12 weeks in HCV-positive (both treatment na¿ve and experienced including cirrhosis CHILD-A) genotype 1 patients with both seropositive and seronegative arthritis. 2.Evaluate the efficacy of SOF/LDV¿RBV in achieving arthritis remission/improvement, at week 24 after treatment withdrawal. 3.To evaluate HRQOL in a population of CHC patients with chronic arthritis at baseline and at 24 weeks post-treatment. ;Primary end point(s): The remission / improvement of arthritis at the end of antiviral therapy in patients with CHC genotype 1 (both ever- already-treated for the infection HCV) with or without cirrhosis (CHILD - A) and HIV-positive or HIV-negative chronic arthritis;Timepoint(s) of evaluation of this end point: 24 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ¿ The safety of fixed-dose combination (FDC) SOF / LDV ¿ RBV for 12 weeks in HCV positive patients genotype 1 (both ever- already-treated for the infection HCV) with chronic hepatitis or cirrhosis (CHILD - A ) and chronic arthritis seropositive or seronegative. ¿ The percentage of patients with HCV RNA <LLOQ the 4th and 12th weeks post-treatment (SVR4 and SVR12) ¿ The percentage of subjects with improvement of arthritis during treatment at weeks 4, 8 and 12) ¿ proportion of patients with treatment failure (non-responders) ¿ analysis of HRQOL (quality of life) at baseline, at the end of treatment and at 24 weeks post-treatment. the measurement points will be gathered which relate to the presence / absence of psychiatric symptoms, severity and quality of psychiatric symptoms, where reliability is ensured. Particular attention will be paid to psychiatric and psychological disorders pre-existing and will be recorded at the time of the visit;Timepoint(s) of evaluation of this end point: 24 weeks. | — |
Countries
Italy
Contacts
Public ContactProgramma Dipartimentale ITEC- Prof
AOU di Bologna-Policlinico S.Orsola-Malpighi
Outcome results
None listed