Safety and Efficacy of Oral Deferasirox in Patients With Porphyria Cutanea Tarda
Safety and Efficacy of Oral Deferasirox in Patients With Porphyria Cutanea Tarda
While clinical phlebotomy is current standard practice for alleviating non-transfusion iron
 overload in patients with PCT, it may not be suitable for all patients. For example, some
 patients are unwilling to be adequately phlebotomized because of inconvenience, as phlebotomy
 can be cumbersome, especially during the induction treatment phase requiring frequent clinic
 visits (twice a month, for at least 6 months) or because of venous access difficulties. Other
 patients are unable to undergo phlebotomy due to medical reasons such as anemia or
 cardiopulmonary disorders. It is postulated such patients with PCT who have non-transfusion
 iron overload could benefit from treatment with deferasirox (Exjade®), a once daily oral iron
 chelator licensed in several countries, including the EU, for treating transfusion iron
 overload in adult and pediatric patients. Although there is some data on the efficacy and
 safety of deferasirox in patients with HH, who, like those with PCT, have non-transfusional
 iron overload, there is a need to evaluate the safety and efficacy of deferasirox treatment
 of non-transfusion iron overload in patients with PCT.
The primary objective is to assess the safety of deferasirox in treating non-transfusion iron
 overload in patients with PCT.

 The secondary objective is to assess the effectiveness of deferasirox treatment :

 After 3 and 6 months to:

 •Lower serum ferritin from abnormal to normal standard ranges specified for males and females
 in this patient population.

 After 6 months to :

 •Lower liver iron content after 24 weeks of treatment measured by liver MRI T2

 After 3 and 6 months to :

 -  Improve clinical symptoms, i.e. improvement in skin lesions (reduction or no new bullae
 formation), and skin fragility (photographs will be used).

 -  Reduce porphyrin levels.
Inclusion Criteria:

 -  Male and female diagnosed with clinically overt Porphyria Cutanea Tarda, sporadic or
 familial as per the European Porphyria Network guidelines i.e. increased urinary and
 plasma porphyrins and faecal isocoproporphyrin detected by fluorescence emission
 spectroscopy,

 -  Skin fragility and bullae lesions,

 -  Age ≥ 18 years old,

 -  non-transfusion iron overload as depicted by a serum ferritin value ≥ 300 μg/L
 for men and ≥ 200 μg/L for women, and/or LIC ≥ 2 mg Fe/g dw for both men and
 women and with transferrin saturation ≥ 45%,

 -  Adequate liver function i.e. ALAT/ASAT and Alkaline Phosphatase ? 2.5 times ULN,
 bilirubin < 1.5 times ULN,

 -  Signed informed consent prior to beginning the specific procedures of the
 protocol,

 -  Ability to comply with all study-related procedures, medications, and
 evaluations,

 -  Sexually active women must use an effective method of contraception, or must have
 undergone clinically documented total hysterectomy and/or oophorectomy, or tubal
 ligation or be postmenopausal (defined as amenorrhea for at least 12 months).
 Since hormonal therapy may cause PCT, oral contraceptives will not be started
 during the course of the study and patients already on oral contraceptives will
 be advised to speak to their physician about discontinuing them and will not be
 enrolled in the study.

 Exclusion Criteria:

 -  Clinical evidence of active Hepatitis B (positive HBsAg with negative HBsAb) and/or
 hepatitis C (positive HCV antibody and detectable HCV RNA with ALT above the normal
 range)

 -  Patients with on going alcoholic dependency > 60g/day

 -  Serum creatinine above the ULN

 -  Creatinine clearance < 60 ml/min, estimated according to Cockcroft-Gault formula
 or MDRD formula for adults

 -  Significant proteinuria as indicated by a urine protein: urine creatinine ratio >
 0.5 mg/mg in a non-first void urine sample.

 -  Diabetes

 -  Iron overload due to hereditary hemochromatosis

 -  History of blood transfusion during the 6 months prior to study entry,

 -  Males with hemoglobin <13 mg/dL, females with hemoglobin <12 mg/dL

 -  Active peptic ulcus

 -  Treatment with phlebotomy within 2 weeks of screening visit

 -  Prior Desferal® treatment within 1 month of the screening visit

 -  Patients currently or previously treated with deferiprone or deferasirox

 -  Patients with a diagnosis of a clinically relevant cataract or a previous history
 of clinically relevant ocular toxicity related to iron chelation

 -  Patient with clinically significant decrease of hearing

 -  Pregnant or lactating women or women of childbearing potential not using adequate
 contraception (pregnancy test mandatory and negative for patient with
 childbearing potential)

 -  Known hypersensitivity to the active ingredient of deferasirox or any excipients

 -  Contraindication to the administration of deferasirox as outlined in the approved
 prescribing information.

 -  Presence of a surgical or medical condition that might significantly alter the
 absorption, distribution, metabolism or excretion of deferasirox

 -  Presence of a non-controlled severe disease affected vital organs as cardiac
 and/or pulmonary disease

 -  Patients with a known diagnosis of cirrhosis (confirmed by biopsy)

 -  Patients with active inflammatory diseases that may interfere with the accurate
 measurement of serum ferritin

 -  Patients treated with systemic investigational drug within 4 weeks prior or with
 topical investigational drug within 7 days prior to the screening visit