A Protocol to Allow Treatment With ICL670 for Patients With or at Risk of Life-threatening Complications of Transfusional Iron Overload Who Are Unable to Tolerate Other Iron Chelators Because of Documented Severe Toxicity

Transfusional Iron Overload Clinical Trial

Official title:

A Protocol to Allow Treatment With ICL670 for Patients With or at Risk of Life-threatening Complications of Transfusional Iron Overload Who Are Unable to Tolerate Other Iron Chelators Because of Documented Severe Toxicity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01044186
• Other study ID #: CICL670A0117
• Secondary ID: 2004-002303-32 E
• Status: Completed
• Phase: Phase 2
• First received: January 5, 2010
• Last updated: February 21, 2017
• Start date: June 2003

Study information

• Verified date: February 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this open-label, non-comparative, multi-center protocol was to further evaluate safety and to provide treatment with ICL670 to patients who had or were at risk of life threatening complications due to transfusional iron overload with a documented inability to tolerate any of the commercially available iron chelators due to severe toxicity rendering continued therapy either impossible or hazardous. Patients who were also ineligible for all on-going registration trials with ICL670 were included in the study. In exceptional cases, patients with a degree of iron overload which was not immediately life-threatening and who were ineligible for the registration trials were also enrolled provided they had a well-documented, sound justification for alternative chelation therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

Inclusion Criteria:

• Patients had to be at risk of life-threatening complications due to transfusional iron overload and be unable to tolerate therapy with any of the commercially available iron chelators (mainly deferoxamine and/or deferiprone) because of documented severe toxicity.

• Patients with a degree of iron overload which was not immediately life-threatening and who were ineligible for other trials with ICL670 could also be enrolled providing they had a well-documented, sound justification for alternative chelation therapy.

• Serum ferritin = 8000 µg/L.

• Serum ferritin < 8000µg/L and LIC of = 7 mg Fe/g dry weight.

• Patients for whom = 8 blood transfusions per year were required in order to maintain the Hemoglobin level at > 9 g/dL.

• Female patients who have reached menarche and who were sexually active had to use double barrier contraception (oral plus barrier contraception), or had to have undergone total hysterectomy and/or ovariectomy, or tubal ligation.

• Written, voluntary informed consent.

Exclusion Criteria:

• Patients with transfusional iron overload who were not experiencing severe toxicities during therapy with other iron chelators (e.g. deferoxamine and/or deferiprone).

• Patients with non-transfusional hemosiderosis.

• Patients with severe liver failure as defined by a score of = 10 points on the Child-Pugh scale.

• Patients with serum creatinine 1.5 times the upper limit of normal (ULN) at screening.

• Patients with a history of nephrotic syndrome.

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

• Patients with severe systemic diseases unrelated to iron overload and which would prevent them from undergoing treatment with ICL670.

• Patients with psychiatric or addictive disorders which prevent them from giving informed consent or undergoing treatment with ICL670.

• Pregnant or breast feeding patients.

• Patients treated with systemic investigational drugs within the past four weeks or topical investigational drugs within the past seven days.

• Any surgical or medical condition which might significantly alter the absorption or excretion of drugs as shown by evidence of any of the following:

• History of inflammatory bowel disease

• History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection

• History of pancreatic injury or pancreatitis; indication of impaired pancreatic function/injury as indicated by abnormal lipase or amylase

• Patients being considered by the investigator as potentially unreliable and/or not cooperative with regard to the protocol.

• History of drug or alcohol abuse within the 12 months prior to dosing.

Related Conditions & MeSH terms

• Iron Overload
• Transfusional Iron Overload

Intervention

Drug:
• ICL670

Locations

Country	Name	City	State
Greece	Novartis investigative Site	Athens
Italy	Novartis Investigative Site	Ancona
Italy	Novartis Investigative Site	Brindisi
Italy	Novartis Investigative Site	Cagliari
Italy	Novartis Investigative Site	Cosenza
Italy	Novartis Investigative Site	Firenze
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Modena
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Torino
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Cincinnatti Children's Hospital Medical center	Cincinnatti	Ohio
United States	Novartis Investigative Site	Houston	Texas
United States	Queens Hospital Center	Jamaica	New York
United States	New York Methodist Hospital	New York	New York
United States	New York Presbyterian Hospital/Weill Medical College of Cornell University	New York	New York
United States	Children's Hospital and Research Center - Oakland	Oakland	California
United States	Children's Hospital of Orange County	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Greece,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the safety profile and to provide treatment with ICL670 for patients with or at risk of life-threatening complications due to transfusional iron overload who are unable to tolerate other iron chelators because of documented severe toxicity.		0 - 163 weeks
Secondary	To estimate the absolute and relative change of liver iron concentration (LIC), to be measured using appropriate methodology available at individual centers.		Yearly
Secondary	To evaluate the role of serum ferritin, serum iron, transferrin and transferrin saturation in monitoring iron burden in these patients.		Quarterly
Secondary	To evaluate the relationship between changes in LIC and serum ferritin, transferring saturation and serum iron.		Yearly

External Links

•   Link
•   Results for CICL670A0117 from Novartis Clinical Trials Website