Treatment of Iron Overload Requiring Chelation Therapy

NCT01927913 | Withdrawn Phase 2 DMC

• 3 other identifiers: SPD602-204FBS0701 (SSP-004184)2013-000743-33
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Transfusional Iron Overload; Iron Overload; Iron Chelation; Beta-thalassemia; Transfusional Hemosiderosis; Iron Metabolism Disorders; Metabolic Diseases

Outcome Measures

Primary Outcomes (1)

• Change in Liver Iron Concentration (LIC) from Baseline Utilizing R2 Magnetic Resonance Imaging (MRI)

  48 Weeks

Secondary Outcomes (7)

• Response Rate Utilizing R2* MRI

  48 weeks

• Change in Cardiac Iron Concentration (CIC) from baseline Utilizing T2* MRI

  48 weeks

• Change in Serum Ferritin Levels from Baseline

  48 weeks

• Change in Pancreas Iron Concentration (PIC) from Baseline Utilizing R2* MRI

  48 weeks

• Left Ventricular Ejection Fraction (LVEF) Utilizing MRI

  48 weeks

Study Arms (2)

SPD602

EXPERIMENTAL

Drug: SPD602

Deferasirox

ACTIVE COMPARATOR

Drug: Deferasirox

Interventions

SPD602 DRUG

32, 50 or 75 mg/kg/day BID, capsule

Also known as: SSP-004184AQ

SPD602

Deferasirox DRUG

Per approved country specific label

Also known as: Exjade®

Deferasirox

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Post-menopausal (12 consecutive months of spontaneous amenorrhea)
• Surgically sterile, or
• 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.
• \. 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Related Publications (1)

• Padhani ZA, Gangwani MK, Sadaf A, Hasan B, Colan S, Alvi N, Das JK. Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. Cochrane Database Syst Rev. 2023 Nov 17;11(11):CD011626. doi: 10.1002/14651858.CD011626.pub3.

  PMID: 37975597 DERIVED

MeSH Terms

Conditions

Iron Overload; beta-Thalassemia; Iron Metabolism Disorders; Metabolic Diseases

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2013
• First Posted: August 23, 2013
• Study Start: November 20, 2014
• Primary Completion: October 30, 2015
• Study Completion: October 30, 2015
• Last Updated: June 2, 2021

Record last verified: 2021-05