Safety, Efficacy and Pharmacokinetics of an Oral Iron Chelator Given for a Year to Pediatric Patients With Iron Overload

This study has been terminated.
(This study was terminated due to treatment stop resulting in an inability to draw conclusions from the data. Evaluation of nonclinical rat findings is ongoing.)
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01363908
First received: May 30, 2011
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

This is an open-label study to assess the pharmacokinetics, safety, efficacy and tolerability of SSP-004184AQ. The study consists of two phases: the pharmacokinetic phase, using a single 16 mg/kg dose of SSP-004184AQ; and the chronic dosing phase, during which patients will receive an additional 48 weeks of SSP-004184AQ dosing. Two age groups will be studied: 6-<12, and 12-<18 years old. The study is designed to initially assess the pharmacokinetics and safety of SSP-004184AQ in older children (adolescents, 12-<18 years old) and then if deemed safe, in younger children (6-<12 years old).


Condition Intervention Phase
Transfusional Iron Overload
Beta-Thalassemia
Drug: SPD602
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open Label, Multi-Center, Single-Dose Pharmacokinetics, and Multiple Dose Study of the Safety, Efficacy and Tolerability of SSP-004184 (SPD602) in a Pediatric Population With Transfusional Iron Overload

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Single-dose Pharmacokinetics: The concentrations of FBS0701 will be measured in plasma from all patients using a validated assay method. Pharmacokinetic parameters will be tabulated and summarized. [ Time Frame: 8 days ] [ Designated as safety issue: Yes ]
    Plasma levels, half-life of SSP-004184AQ and other pharmacokinetic parameters following a single capsule dose of SSP-004184AQ at 16 mg/kg with 7 days of follow-up.

  • Multiple Dose SSP-004184AQ Study: Safety and Tolerability Based on Clinical Assessments; Efficacy Based on Clinical Response [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Clinical assessments include incidence and severity of adverse events, physical examinations including vital signs, clinical laboratory values, and ECGs); clinical response to be evaluated based on changes in liver and cardiac iron concentration determined by MRI in patients able to be studied using this method; serum ferritin in all patients.


Enrollment: 30
Study Start Date: August 2011
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SPD602 (26 mg/kg)
Oral SSP-004184AQ taken once daily for 48 weeks
Drug: SPD602
Other Name: SSP-004184, deferitazole
Experimental: SPD602 (36 mg/kg)
Oral SSP-004184AQ taken once daily for 48 weeks. Starting dose based on transfusion burden and iron overload status. Doses may range from 8-60mg/kg/day depending on clinical response.
Drug: SPD602
Other Name: SSP-004184, deferitazole
Experimental: SPD602 (16 mg/kg)
A single dose given in the initial pharmacokinetic phase.
Drug: SPD602
Other Name: SSP-004184, deferitazole

Detailed Description:

Pharmacokinetic Phase: Patients will receive a single 16 mg/kg dose of SSP-004184AQ in capsule form.

Chronic Dosing Phase: Patients will receive SSP-004184AQ capsules daily for 48 weeks. Doses may range from 8-60 mg/kg/d.

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Parents willing and able to sign the approved informed consent for their children and subjects between the ages of 6 and <18 years willing and able to provide their assent (based on institutional guidelines).
  • Able to swallow whole capsules.
  • Age >6 and <18 years.
  • Transfusion-dependent subjects who have transfusional iron overload requiring chronic treatment with deferoxamine, deferasirox, or deferiprone. A transfusion dependent subject is defined in this study as one with a minimum transfusion history totaling more than 20 units of packed red blood cells OR a calculated iron load based on transfusion history of 200mg/kg AND a transfusion requirement of 7 or more transfusions per year; or, in subjects with sickle cell anemia, be iron overloaded but can be receiving transfusion exchange therapy in lieu of transfusions.
  • In the opinion of the Investigator (and in consultation with the subject's parents), the subject is able to discontinue all existing iron chelation therapies for a minimum period of 1-5 days prior first dose of SSP-004184AQ, for the initial pharmacokinetic period of 8 days (if applicable), and for up to 49 weeks if continuing into the chronic dosing phase.
  • Subjects able to have an MRI must have:

    1. liver iron concentration >2 and <30mg/g (dry weight, liver) by FerriScan® R2
    2. cardiac MRI T2* >10ms (Note: Subjects not able to have an MRI will be considered iron overloaded on the basis of serum ferritin only.)
  • Serum ferritin >500ng/mL at Screening.
  • Mean of the previous 3 pre-transfusion hemoglobin concentrations greater than or equal to 7.5g/dL.
  • If appropriate, depending on age, female subjects of child-bearing potential need to use a medically acceptable method for birth control from screening until 30 days after the last dose of the study drug. Females of child-bearing potential must have a negative serum beta-HCG pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit. Females of child-bearing potential must agree to abstain from sexual activity that could result in pregnancy or agree to use acceptable methods of contraception.

Exclusion Criteria

  • As a result of medical review, physical examination (including height and weight) or Screening investigations, the Principal Investigator considers the subject unfit for the study.
  • Iron overload from causes other than transfusional hemosiderosis.
  • Severe cardiac dysfunction.
  • Non-elective hospitalization within the 30 days prior to Baseline testing.
  • Evidence of clinically significant oral, cardiovascular, gastrointestinal, hepatic, biliary, renal, endocrine, pulmonary, neurologic, psychiatric, or skin disorder that contra-indicates dosing with SSP-004184AQ.
  • Evidence of significant renal insufficiency, eg, serum creatinine above the upper limit of normal or proteinuria greater than 1 gm per day.
  • Known sensitivity to any ingredient in the SSP-004184AQ formulation.
  • Platelet count below 100,000/µL or absolute neutrophil count less than 1500/mm3 at Screening.
  • ALT >180 IU/L at Screening.
  • Use of any investigational agent within the 30 days prior to Baseline testing.
  • Pregnant or lactating females.
  • Cardiac left ventricular ejection fraction a) Below the locally determined normal range in the 12 months prior to screening by echocardiography or MRI or <50% at Baseline testing by MRI (echocardiograph is acceptable for LVEF if MRI information is not available).
  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: NCT01363908

Locations
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Canada, Ontario
Toronto Sick Kids Hospital
Toronto, Ontario, Canada
Italy
Ospedale Regionale Mecrocitemie
Cagliari, Italy, 09121
Centro della Microcitemia e delle Anemie Congenite
Genoa, Italy
Thalassemia Center San Luigi Hospital
Orbassano, Italy
Lebanon
American University of Beirut Medical Center
Beirut, Lebanon
Chronic Care Center
Beirut, Lebanon
Turkey
Ege University Hospital
Izmir, Turkey, 35100
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Ellis J Neufeld, M.D. Children's Hospital Boston
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01363908     History of Changes
Other Study ID Numbers: SPD602-202, SSP-004184AQ
Study First Received: May 30, 2011
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Shire:
Beta-Thalassemia
Sickle Cell Anemia
Transfusional iron overload
Iron Overload
Iron Chelation

Additional relevant MeSH terms:
Thalassemia
Iron Overload
Beta-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Iron Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on September 22, 2014