Study of Deferasirox Relative to Subcutaneous Deferoxamine in Sickle Cell Disease Patients

Sickle Cell Disease Clinical Trial

Official title:

A Randomized, Open-label, Multi-center, Phase II Study to Evaluate the Safety and Efficacy of Deferasirox (ICL670) 20 mg/kg/Day Relative to Subcutaneous Deferoxamine in Sickle Cell Disease Patients With Iron Overload From Repeated Blood Transfusions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00110617
• Other study ID #: CICL670A2201
• Status: Completed
• Phase: Phase 2
• First received: May 10, 2005
• Last updated: May 23, 2011
• Start date: May 2005
• Est. completion date: April 2008

Study information

• Verified date: May 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will examine the long-term safety and efficacy of Deferasirox in patients with sickle cell disease and iron overload from repeated blood transfusions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 212
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

Inclusion Criteria:

• Age greater than or equal to 2 years

• Male or female patients with sickle cell disease (SS, SC, SD, Sßo or Sß+ thalassemia)

• Iron overload from repeated blood transfusion, as defined by one of the following:

1. For patients > 16 years old receiving simple transfusions: lifetime history of receipt of at least 120 ml/kg or 30 adult units of packed red blood cells, OR

2. For patients = 16 years old receiving simple transfusions: lifetime history of receipt of at least 120 ml/kg of packed red blood cells, OR

3. For all patients receiving exchange transfusions in the absence of a previous attempt to achieve negative iron balance: lifetime performance of at least 20 procedures, OR

4. For all patients: liver iron content = 7 mg Fe/g dry weight as measured by biopsy, Magnetic Resonance Imaging (MRI), or magnetic susceptibility performed within 3 months prior to entry into screening

• For entry into the screening period: serum ferritin of = 1000 µg/mL on at least two occasions during the prior year obtained in the absence of concomitant infection.

• Body weight > 10 kg

• No known allergy or contraindication to the administration of deferoxamine

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

• Sexually active pre-menopausal female patients must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months.

• Written informed consent by the patient or for pediatric patient's consent of the patient's legal guardian. The definition of the term 'pediatric' for enrollment and study conduct will be in accordance with the local legislation.

Exclusion Criteria:

• Serum creatinine above the upper limit of normal

• Significant proteinuria

• History of nephrotic syndrome

• Alanine aminotransferase (ALT) = 250 U/L at screening

• Clinical evidence of active hepatitis B or hepatitis C

• History of HIV

• Fever or other signs/symptoms of infection within 10 days prior to the screening visit

• Uncontrolled systemic hypertension

• History of Myocardial Infarction, Congestive Heart Failure or unstable cardiac disease not controlled by standard medical therapy

• Clinically relevant cataract or a previous history of clinically relevant ocular toxicity related to iron chelation

• Presence of a surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of any study drug

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

• Pregnant or breast feeding patients

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

• Randomization in a previous clinical trial involving ICL670

Other protocol-related inclusion / exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Hemolytic
• Anemia, Sickle Cell
• Hemolytic Anemia
• Iron Overload
• Sickle Cell Disease

Intervention

Drug:
• Deferasirox (ICL670)
Deferasirox was provided in 125 mg, 250 mg, and 500 mg dispersible tablets and was administered orally at an initial dose of 20 mg/kg/day.
• Deferoxamine (DFO)
Deferoxamine was supplied in vials of 500 mg and 2000 mg administered subcutaneously for a weekly dose of 175 mg/kg.

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta
Canada	Hopital Ste-Justine	Montreal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
United States	University of Michigan	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta at Scottish Rite	Atlanta	Georgia
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Adult Sickle Cell Clinic	Augusta	Georgia
United States	St. Jude Children's Hospital Affiliate	Baton Rouge	Louisiana
United States	University of Alabama Medical center	Birmingham	Alabama
United States	University of Alabama Pediatric Hematology/Oncology	Birmingham	Alabama
United States	Brigham and Woman's Hospital/Harvard Medical School	Boston	Massachusetts
United States	Children's Hospital	Boston	Massachusetts
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Sickle Cell Center, Montefiore Hospital	Bronx	New York
United States	New York Methodist Hospital	Brooklyn	New York
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Carolinas Medical Transplant Center	Charlotte	North Carolina
United States	Children's Memorial Hospital	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Liberty Hematology Oncology Center	Columbia	South Carolina
United States	Palmetto Health Clinical Trials	Columbia	South Carolina
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Cooks Children's Hospital	Fort Worth	Texas
United States	Texas Children's Hospital/Baylor College of Medicine	Houston	Texas
United States	Pediatric Sickle Cell Program/James Whitcomb Riley Hospital for Children	Indianapolis	Indiana
United States	Loma Linda University Medical Center	Loma Linda	California
United States	St Jude's Children's Research Hospital	Memphis	Tennessee
United States	St. Jude's Children Research Hospital	Memphis	Tennessee
United States	Miami Children's Hospital	Miami	Florida
United States	University of South Alabama	Mobile	Alabama
United States	University of South Alabama Medical Center	Mobile	Alabama
United States	Children's Hospital	New Orleans	Louisiana
United States	Tulane University Sickle Cell Center	New Orleans	Louisiana
United States	Columbia University	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Children's Hospital of the King's Daughter	Norfolk	Virginia
United States	Children's Hospital Oakland	Oakland	California
United States	The University of Oklahoma	Oklahoma City	Oklahoma
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Jefferson University	Philadelphia	Pennsylvania
United States	Pennsylvania Oncology/Hematology	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Medical College of Virginia	Richmond	Virginia
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Backus Children's Hospital	Savannah	Georgia
United States	LSU Health Sciences Center/Carroll W. Feist Professor of Cancer Research	Shreveport	Louisiana
United States	Washington University School of Medicine	St. Louis	Missouri
United States	Santee Hematology/Oncology	Sumter	South Carolina
United States	H. Lee Muffit Cancer Center and Research Institute/James A. Haley Veterans Hospital	Tampa	Florida
United States	Tampa Children's Hospital at St Joseph's	Tampa	Florida
United States	Tampa Children's Hospital at St. Joseph's	Tampa	Florida
United States	Scott and White Memorial Hospital & Clinics	Temple	Texas
United States	Center for Cancer and Blood Disorders	Washington	District of Columbia
United States	Children's National Medical Center	Washington	District of Columbia
United States	Howard University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Number of Participants With Adverse Events (AEs) in the First 24 Weeks of Treatment	The number of participants with Adverse Events (AEs) overall and according to Medical Dictionary for Regulatory Activities (MedDRA) preferred term greater than or equal to 5% participants in any group by treatment in the first 24 weeks.	24 Weeks	Yes
Secondary	Absolute Change in Serum Ferritin From Baseline to Week 24	Absolute change from baseline serum ferritin after 24 weeks of treatment with Deferasirox (ICL670) and absolute change from baseline serum ferritin after 24 weeks of treatment with Deferoxamine. Means were adjusted for the amount of transfused blood.	Baseline, 24 Weeks	No
Secondary	Absolute Change in Serum Ferritin After Start of Treatment With Deferasirox (ICL670) to Week 24 and to Week 52	Absolute change in serum ferritin after start of treatment with Deferasirox (ICL670) to week 24 and the absolute change in serum ferritin after start of treatment with Deferasirox (ICL670) to week 52 for the Deferasirox treatment group and the Deferoxamine then Deferasirox treatment group. Means were adjusted for the amount of transfused blood.	Start of Deferasirox (ICL670) treatment, 24 Weeks, 52 Weeks	No
Secondary	Absolute Change in Serum Ferritin After Start of Treatment With Deferasirox (ICL670) to Week 104	Absolute change in serum ferritin after start of treatment with Deferasirox (ICL670) to week 104 for the Deferasirox treatment group. Means were adjusted for the amount of transfused blood.	Start of Deferasirox (ICL670) treatment, 104 Weeks	No

External Links

•   Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.