Hereditary Hemochromatosis MedDRA version: 20.0 Level: LLT Classification code 10057874 Term: Hereditary hemochromatosis System Organ Class: 100000004850
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female = 18-years-old - Documented genotype testing confirming homozygous for the C282Y mutation (C282Y/C282Y) - Transferrin saturation = 45% (at either screening visit) - Serum Ferritin = 500 µg/L (at either screening visit) 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 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Medical conditions that preclude inclusion: - Iron overload not due to HH - Condition which might significantly alter the absorption, distribution, metabolism or excretion of oral deferasirox - Systemic disease which prevents taking study treatment or any contraindication to phlebotomy - Inflammatory condition or immunological disease which may interfere with the SF interpretation, such as an active infection, collagen vascular disorders, irritable bowel syndrome, lupus, or immune thrombocytopenia - Significantly impaired gastrointestinal function or disease that may significantly alter the absorption of oral deferasirox, e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption Hepatocellular carcinoma at any time is excluded. 2. Prior iron chelation therapy, prohibited concomitant medications with deferasirox syndrome, or small bowel resection. - Psychiatric or addictive disorder which prevent giving informed consent or undergoing any of the treatment options or unwilling or unable to comply with the protocol - Uncontrolled or significant cardiac disease or symptomatic cardiac arrhythmias, e.g., sustained ventricular tachycardia and clinically significant second or third degree AV block without a pacemaker - Illicit drug use and/or alcohol use, defined as an average alcohol consumption greater than one standard drink a day for women or two standard drinks a day for men within the 12 months prior to enrolment. - Cirrhosis, including Child-Pugh class A, B, and C, diagnosed by liver biopsy, elastography, radiologic exams, or clinical criteria. - Active hepatitis B or C (hepatitis B carrier will be allowed) - History of HIV seropositivity (ELISA or Western blot) - Malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, except localized basal cell carcinoma of the skin, or any history of hepatocellular carcinoma 3. Abnormal laboratory values 4. Participation in an investigational study: - Observational registry study is allowable - Within 30 days prior to enrollment or within 5-half-lives of an investigational product, whichever is longer - Treatment with a systemic investigational drug within 4 weeks or topical investigational drug within 7 days of starting the study 5. Pregnancy and contraception: - Pregnant or nursing (lactating) women - Women of child-bearing potential unless using appropriate methods of contraception. Deferasirox may reduce the efficacy of hormonal contraception, thus it is recommended to use alternative methods of contraception. - Post-menopausal and not of childbearing potential if she has had 12 months of natural (spontaneous) amenorrhea with an expected clinical profile
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess the response rate in the deferasirox FCT and phlebotomy treatment arms where response is defined by achieving target SF = 100 µg/L on or before 24 months;Secondary Objective: Key secondary: Characterize the ocular safety of deferasirox FCT and phlebotomy over 24 months Other secondary: - Evaluate the safety and tolerability of deferasirox FCT and phlebotomy over 24 months. - Assess the change from baseline in visual acuity, intra-ocular pressure, retina or/and optic nerve abnormalities, and lens abnormalities at months 6, 12, 18, and 24 of deferasirox FCT and phlebotomy. - Assess the safety and tolerability of deferasirox FCT in patients who interrupt and re-initiate treatment due to SF = 100 µg/L and = 300 µg/L - Assess the first time to response (defined as SF = 100 µg/L) between the deferasirox and phlebotomy treatment groups ;Primary end point(s): Proportion of patients achieving target SF = 100 µg/L for the first time;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary: Incidence of ocular AEs overall and by severity, type of AE, and relation to study treatment Other secondary: - Incidence of AEs, AEs leading to discontinuation from study, laboratory abnormalities, and deaths - Change from baseline at months 6, 12, 18 and 24 in visual acuity, tonometry, slit lamp, and fundus exams - Incidence of AEs in patients who interrupt due to reaching target SF = 100 µg/L, then re-initiate therapy at = 300 µg/L - Time to reach target SF = 100 µg/L in the deferasirox and phlebotomy arms for the first time;Timepoint(s) of evaluation of this end point: - 24 months - 24 months - 6, 12, 18 and 24 months - 24 months - 24 months | — |
Countries
Belgium, France, Germany, Romania, Russian Federation, Slovakia, Spain, Switzerland, United States
Contacts
Public ContactDRA information desk
Novartis Slovakia s.r.o.
Outcome results
None listed