Safety and Efficacy of Oral Deferasirox in Patients With Porphyria Cutanea Tarda

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2011 by Assistance Publique - Hôpitaux de Paris.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Association pour l'Etude des Fonctions Digestives (AEFD)
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01284946
First received: January 26, 2011
Last updated: NA
Last verified: January 2011
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Porphyria Cutanea Tarda
Drug: Exjade
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Open Label Clinical Trial Exploring the Safety and the Efficacy of Oral Deferasirox in Patients Newly Diagnosed With Porphyria Cutanea Tarda (PCT) and Non-transfusion Iron Overload

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • The primary objective is to assess the safety of deferasirox in treating non-transfusion iron overload in patients with PCT. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Related drug adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Incidence type and severity of drug related adverse events


Secondary Outcome Measures:
  • The change from baseline in serum ferritin after 12 and 24 weeks of treatment,The change from baseline in iron burden after 24 weeks of treatment measured by liver MRI T2,The evolution of clinical symptoms [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Chage from baseline in serum ferritin, iron burden, improvement in clincal symptoms, porphyrin levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: January 2011
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exjade
Safety and efficacy
Drug: Exjade
Orodispersible Tablet, 10 mg/Kg/day ± 5 mg/Kg/day during 24 weeks Deferasirox should be taken daily 30 minutes before breakfast
Other Name: DEFERASIROX

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01284946

Contacts
Contact: Benoit Coffin, Professor 33147606061 benoit.coffin@lmr.aphp.fr

Locations
France
Hopital Louis Mourier, GI unit, Recruiting
Colombes, Ile de France, France, 92700
Contact: Benoit Coffin, Professor    33147606061    benoit.coffin@lmr.aphp.fr   
Principal Investigator: Deybach Jean-Charles, Professor         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Association pour l'Etude des Fonctions Digestives (AEFD)
Investigators
Principal Investigator: Deybach Jean-Charles, Professor Assistance Publique - Hôpitaux de Paris
  More Information

Publications:
Responsible Party: COFFIN, Association pour l'Etude des Fonctions Digestives
ClinicalTrials.gov Identifier: NCT01284946     History of Changes
Other Study ID Numbers: AEFD2010-01
Study First Received: January 26, 2011
Last Updated: January 26, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Assistance Publique - Hôpitaux de Paris:
PCT sporadic or familial
Skin fragility and bullae lesions
non-transfusion iron overload

Additional relevant MeSH terms:
Porphyrias
Porphyria, Erythropoietic
Porphyria Cutanea Tarda
Porphyrias, Hepatic
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Skin Diseases, Metabolic
Skin Diseases
Metabolic Diseases
Skin Diseases, Genetic
Liver Diseases
Digestive System Diseases
Deferasirox
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014