Safety and Pharmacodynamic Study of an Oral Iron Chelator Given for 6 Months to Patients With Iron Overload

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01186419
First received: August 19, 2010
Last updated: May 17, 2013
Last verified: May 2013
  Purpose

The purpose of this research study is to evaluate the safety of two doses of FBS0701, a new oral iron chelator, and its effectiveness in clearing iron from the liver. FBS0701 is a medication taken by mouth that causes the body to get rid of iron. Iron chelators are used in patients with β-thalassemia and other forms of anemia who experience iron overload - iron increases in the body as a result of regularly required blood transfusions. Patients who qualify will be randomized to receive one of two doses of FBS0701 for up to 24 weeks (6 months) with a total study duration of up to 33 weeks. These patients will be eligible to participate in a dosing extension for up to 72 weeks. The maximum duration of dosing will be up to 96 weeks. The safety of patients will be monitored frequently during the study by physical exams, ECGs, and blood tests. To assess the amount of iron in the liver and heart, each patient must undergo 6 MRI scans during the study. Patients will not need to stay in the hospital for this study but will need to visit the outpatient clinic up to 28 times over the 96 week period. Patients currently taking an iron chelator will be required to stop for a total of up to 26 weeks. The results of this study will help to determine if FBS0701 may be effective as an iron chelator.


Condition Intervention Phase
Transfusional Iron Overload
Beta-thalassemia
Drug: SPD602 (FBS0701, SSP-004184)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, 24 Week, Randomized, Open Label, Multi-Center Study to Assess the Safety, Tolerability, and Pharmacodynamics of FBS0701 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy, With a 72 Week Dosing Extension

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Safety and Tolerability based on clinical assessments (AEs, ECGs, Physical Exam, Clinical Laboratory tests) [ Time Frame: 96 weeks (24 weeks of dosing and up to a 72 week dosing extension) ] [ Designated as safety issue: Yes ]
  • Changes in liver iron concentration by MRI [ Time Frame: up to 96 weeks (Baseline, week 12, week 24, week 48 and week 96.) ] [ Designated as safety issue: No ]
  • Assess the safety and pharmacodynamic activity of FBS0701 when administered daily for up to 96 weeks [ Time Frame: up to 96 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assess the steady state pharmacokinetics of FBS0701 in a subset of patients [ Time Frame: up to 96 weeks ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: August 2010
Study Completion Date: January 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SPD602 (16mg) Drug: SPD602 (FBS0701, SSP-004184)
Oral FBS0701 taken one time daily for up to 96 weeks.
Experimental: SPD602 (32mg) Drug: SPD602 (FBS0701, SSP-004184)
Oral FBS0701 taken one time daily for up to 96 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Transfusional iron overload due to: hereditary anemias such as sickle cell disease, β-thalassemia and Diamond-Blackfan anemia; acquired anemias such as Myelodysplastic Syndrome and other forms of bone marrow failure. Patients must also be transfusion-dependent and require chronic treatment with deferoxamine, deferasirox, and/or deferiprone.
  • Willing to discontinue all existing iron chelation therapies throughout study period.
  • Serum ferritin greater than 500 ng/mL at Screening.
  • Baseline liver iron concentration and cardiac MRI T2* per protocol requirements.
  • Mean of the previous three pre-transfusion hemoglobin concentrations greater than or equal to 7.5 g/dL.
  • Agrees to use an approved method of contraception throughout study period.

Exclusion Criteria:

  • As a result of medical review, physical examination or Screening investigations, the Principal Investigator considers the patient unfit for the study.
  • Non-elective hospitalization within the 30 days prior to Baseline testing. (Patients with sickle cell anemia who are admitted to the hospital for management of sickle crisis pain whose uncomplicated hospital course was four days or less and who, 14 days prior to Baseline testing, have returned to their previous health status are acceptable.)
  • Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow or skin disorder as determined by the Investigator.
  • Evidence of significant renal insufficiency; possible examples include: serum creatinine above the upper limit of normal, proteinuria greater than 2 gm per day or calculated creatinine clearance of less than 60 mL/minute.
  • Cardiac left ventricular ejection fraction outside of protocol requirements.
  • Known sensitivity to magnesium stearate, croscarmellose sodium or FBS0701.
  • Platelet count below 100,000/µL and/or absolute neutrophil count less than 1500/mm3 at Screening and <50% at Baseline testing by MRI
  • Alkaline phosphatase, AST or ALT outside of protocol requirements.
  • Liver Function Tests: ALT >5 times the local upper limit of normal on two occasions in the previous 12 months or ALT at Screening >200 IU/L
  • Use of any investigational agent within the 30 days prior to the Baseline testing.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01186419

Locations
United States, California
Children's Hospital and Research Center of Oakland
Oakland, California, United States, 94609
United States, Massachusetts
Children's Hospital of Boston
Boston, Massachusetts, United States, 02115
Italy
Ospedale Regionale Microcitemie
Cagliari, Italy
Centro della Microcitemia e delle Anemie Congenite
Genoa, Italy
Thalassemia Center San Luigi Hospital
Orbassano, Italy
Thailand
Siriraj Hospital, Mahidol University
Bangkok, Thailand
Turkey
Pediatric Hematology, Ege University Hospital
Izmir, Turkey
United Kingdom
University College London Hospital
London, United Kingdom
Whittington Hospital
London, United Kingdom
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Ellis J. Neufeld, MD Children's Hospital Boston
  More Information

No publications provided by Shire

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01186419     History of Changes
Other Study ID Numbers: SPD602-201, 2010-019645-25, FBS0701-CTP-04
Study First Received: August 19, 2010
Last Updated: May 17, 2013
Health Authority: United States: Food and Drug Administration
Turkey: Ministry of Health
Italy: Ethics Committee
Thailand: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Shire:
Beta-thalassemia
Sickle cell anemia
Transfusional iron overload
Iron overload
Iron chelation

Additional relevant MeSH terms:
Beta-Thalassemia
Thalassemia
Iron Overload
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Iron Metabolism Disorders
Metabolic Diseases
Iron
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014