Treatment of Iron Overload Requiring Chelation Therapy

This study has been withdrawn prior to enrollment.
(This study was withdrawn until the evaluation of the nonclinical rat findings is complete.)
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01927913
First received: August 20, 2013
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

The purpose of this open-label study is to assess liver iron concentration using MRI imaging in subjects with beta-thalassemia when administered with either SPD602 or deferasirox for the treatment of chronic transfusional iron overload.


Condition Intervention Phase
Transfusional Iron Overload
Iron Overload
Iron Chelation
Beta-thalassemia
Transfusional Hemosiderosis
Iron Metabolism Disorders
Metabolic Diseases
Drug: SPD602
Drug: Deferasirox
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 48-week, Open-label, 2-arm, Parallel-group, Randomized Exploratory Study to Assess Liver Iron Concentration Measured by FerriScan® (R2) Magnetic Resonance Imaging in B-thalassemia Subjects Administered SPD602 (SSP-004184AQ) or Exjade® (Deferasirox) for Treatment of Chronic Transfusional Iron Overload

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Change in Liver Iron Concentration (LIC) from Baseline Utilizing R2 Magnetic Resonance Imaging (MRI) [ Time Frame: 48 Weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response Rate Utilizing R2* MRI [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Change in Cardiac Iron Concentration (CIC) from baseline Utilizing T2* MRI [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Change in Serum Ferritin Levels from Baseline [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Change in Pancreas Iron Concentration (PIC) from Baseline Utilizing R2* MRI [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Left Ventricular Ejection Fraction (LVEF) Utilizing MRI [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Gastrointestinal Symptom Rating Scale [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Total Neuropathy Score nurse (TNSn) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: November 2014
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SPD602 Drug: SPD602
32, 50 or 75 mg/kg/day BID, capsule
Other Name: SSP-004184AQ
Active Comparator: Deferasirox Drug: Deferasirox
Per approved country specific label
Other Name: Exjade®

  Eligibility

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

Inclusion Criteria:

These criteria are to be met at the Screening Visit (Visit 1), the Washout Visit (Visit 2), and the Baseline Visit (Visit 3), if reassessed.

  • An understanding, ability, and willingness to fully comply with study procedures and restrictions.
  • Ability to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent as applicable to participate in the study before completing any study-related procedures.
  • Subjects 18 years of age or older at the time of signing consent.
  • Female subjects should be one of the following:

    1. Post-menopausal (12 consecutive months of spontaneous amenorrhea)
    2. Surgically sterile, or
    3. Females of child-bearing potential must have a negative serum Beta-HCG pregnancy test at the Screening Visit (Visit 1) and a negative urine pregnancy test at the Baseline Visit (Visit 3). 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.
  • Subjects with beta-thalassemia who have received at least 100mL/kg of packed red blood cells (or >20 transfusion units) and who have iron overload (transfusional hemosiderosis) requiring chronic treatment with an iron chelator.
  • Serum ferritin >500µg/L at the Screening Visit (Visit 1).
  • Baseline LIC (last MRI assessment prior to Day 1) greater than or equal to 2.0mg and less than 30.0mg iron per g (equivalent dry weight, liver) determined by FerriScan® R2 MRI.

    8. Mean of the previous 3 pre-transfusion hemoglobin concentrations greater than or equal to 7.5g/dL assessed at the Screening Visit (Visit 1) (1 value from clinical laboratory tests taken at the Screening Visit [Visit 1] and the previous 2 historical values available).

Exclusion Criteria:

  • Severe iron overload including: (a) cardiac T2* MRI less than 10.0ms; or (b) LIC by FerriScan® R2 MRI greater than or equal to 30.0mg/g liver (dw) as assessed at the Screening Visit (Visit 1).
  • Iron overload from causes other than transfusional siderosis.
  • Subjects with thalassemia intermedia
  • Unable to undergo MRI assessment.
  • Cardiac LVEF less than 50% at baseline testing by MRI.
  • Subjects with documented liver failure (presence of portal hypertension, hepatic edema, ascites, cirrhosis), Child-Pugh C hepatic impairment, or biliary disorder.
  • Platelet count <100 x 109/L at the Screening Visit (Visit 1).
  • Absolute neutrophils counts of <1500mm3 at the Screening Visit (Visit 1).
  • Evidence of renal insufficiency eg, creatinine clearance <60mL/min or serum creatinine >1.5x ULN at the Screening Visit (Visit 1).
  • Clinically significant laboratory assessments at the Screening Visit (Visit 1).
  • Significant proteinuria: urinary protein/creatinine ratio >1.0 in a non-first void urine sample at the Screening Visit (Visit 1).
  • Current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments.
  • Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition, including pregnancy, that presents undue risk from the investigational product or procedures.
  • Current use of any medication contraindicated in the deferasirox prescribing information/SmPC.
  • Known or suspected intolerance or hypersensitivity to SSP-004184AQ, deferasirox, closely-related compounds, or any of the stated ingredients in either medication.
  • Known history of alcohol or other substance abuse within the last year.
  • Within 30 days prior to the Baseline Visit (Visit 3):

    1. Have used an investigational product
    2. Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this study.
  • History of malignancy within the past 5 years, with the exception of basal cell or squamous cell skin carcinoma or cervical carcinoma in situ or completely resected colon carcinoma in situ.
  • Insufficient venous access that precludes prescribed blood draws for safety laboratory assessments.
  • Pregnant or lactating females.
  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: NCT01927913

Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Ali Taher, MD, PhD, FRCP American University of Beirut Medical Center
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01927913     History of Changes
Other Study ID Numbers: SPD602-204, FBS0701 (SSP-004184), 2013-000743-33
Study First Received: August 20, 2013
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Beta-Thalassemia
Iron Metabolism Disorders
Hemosiderosis
Metabolic Diseases
Thalassemia
Iron Overload
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Deferasirox
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014