Thalassemia patients with transfusion dependent iron overload and chronic hepatitis C MedDRA version: 15.0 Level: LLT Classification code 10008912 Term: Chronic hepatitis C System Organ Class: 10021881 - Infections and infestations MedDRA version: 15.0 Level: PT Classification code 10043388 Term: Thalassaemia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEGINTERFERON ALFA-2A
CAS Number: 198153-51-4
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 180-
Sponsors
AZIENDA OSPEDALIERA POLICLINICO DI MODENA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age =18 years; - ß-thalassemia patients with transfusional iron overload: Iron overload: ? 20 units (about 100 ml/kg) of packed red blood cells received or when there is evidence from clinical monitoring that chronic iron overload is present (e.g. serum ferritin >1,000 µg/l); - Patients previously treated with any iron chelator (deferoxamine, deferiprone, deferasirox) and already receiving deferasirox at least two months before study start; - Cardiac MRI T2* >15msec; - LVEF at MRI =56%; -Adult male or female patients with diagnosis of chronic hepatitis C (HCV-RNA and HCV-antibodies positivity), any genotype, candidate to antiviral therapy; - Women of childbearing potential should use a valid contraceptive method; - Written Informed Consent obtained from the patient. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 39 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: - Decompensated cirrhosis;- Patients with ALT levels > 10 x ULN;- White-cell count less than 3000 per cubic millimeter;- Neutrophil count less than 1500 per cubic millimeter;- Platelet count less than 90,000 per cubic millimeter;- TSH alterations (with or without HRT);- HBsAg positive / HIV seropositivity (Elisa or Western blot);- HCC or focal hepatic lesions at the ultrasound examination in the 3 months before; - Alcohol abuse (more than 25 grams per day); - Prior organ or HSC transplantation; -Severe psychiatric conditions; - Seizure disorder or other conditions contraindicated to receive peg-IFN and/or Ribavirin, such as history or clinical evidence of chronic pulmonary disease, history of immunologically mediated disease, history of ophthalmologic disorders, history of organ transplantation other than cornea or hair transplant, history of known coagulopathy including hemophilia; - Active cardiovascular disease (heart failure or malignant arrhythmias); - Poorly controlled diabetes mellitus; - Patients with considerable impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral deferasirox (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); - History of galactose intolerance, lactase deficiency or glucose-galactose malabsorption; - History of hypersensitivity to any of the study drugs or to drugs with similar chemical structure; - Received concomitant systemic antibiotics, antifungals or antivirals for the treatment of active infection within 14 days prior to baseline; - Received systemic corticosteroids (prednisone equivalent of >10mg/day) within 14 days prior to baseline; - Active inflammatory disease that may interfere with accurate measurement of serum ferritin; - History of clinically relevant ocular or ear disorders; - Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing any of the treatment options or patients unwilling or unable to comply with the protocol; - History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin; - Pregnant or nursing (lactating) women are not eligible to participate in the study; - Patients participating in another clinical trial or receiving an investigational drug; - History of non-compliance with medical regimens or patients who are considered potentially unreliable and/or not cooperative, unwilling or unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety profile of peg-IFN and RBV in combination with deferasirox, based upon drug administration and reporting of serious adverse events on the first 12 weeks of antiviral treatment.;Secondary Objective: - Safety evaluation for the concomitant use of peg-IFN /RBV + deferasirox, based upon drug administration and reporting of serious adverse events at 24 and 48 wks; - Safety of peg-IFN and RBV in combination with chelation therapy with deferasirox, evaluating all adverse events (AEs), serious adverse events (SAEs) and laboratory abnormalities during the 48 Wks of treatment; - Changes in serum ferritin, transfusion requirements, LIC and cardiac iron content by MRI T2*, cardiac function (LVEF, LVESV, LVEDV and LVMI); - Virological Evaluations: Rapid Virological Response, RVR (Undetectable serum HCV RNA after 4 weeks of therapy), Early Virological Response, EVR (Undetectable serum HCV RNA after 12 weeks of therapy).;Primary end point(s): Incidence, type and severity of SAEs in first 12 weeks.;Timepoint(s) of evaluation of this end point: First 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Incidence, type and severity of SAEs at 24 and 48 weeks; - Incidence, type and severity of AEs, renal, hepatic, biochemistry and hematologic parameters and SAEs during 48 weeks; -Efficacy of chelation therapy: changes in serum ferritin, transfusion requirements, at 12, 24 and 48 weeks and LIC and cardiac iron content by MRI T2* at 48 weeks, cardiac function (LVEF, LVESV, LVEDV and LVMI) at 48 weeks; - HCV RNA assessment after 4 and 12 weeks of therapy.;Timepoint(s) of evaluation of this end point: - at 24 and 48 weeks; - during 48 weeks; - at 12, 24 ,48 weeks and at 48 weeks; - after 4 and 12 weeks. | — |
Countries
Italy
Contacts
Public ContactDipartimento Medico
OPIS s.r.l.
Outcome results
None listed