NCT01186419

Brief Summary

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
51

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Aug 2010

Geographic Reach
5 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 13, 2010

Completed
6 days until next milestone

First Submitted

Initial submission to the registry

August 19, 2010

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 23, 2010

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 8, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 8, 2013

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

June 3, 2015

Completed
Last Updated

June 10, 2021

Status Verified

May 1, 2021

Enrollment Period

2.4 years

First QC Date

August 19, 2010

Results QC Date

April 23, 2015

Last Update Submit

May 30, 2021

Conditions

Transfusional Iron OverloadBeta-thalassemia

Keywords

Beta-thalassemiaSickle cell anemiaTransfusional iron overloadIron overloadIron chelation

Outcome Measures

Primary Outcomes (1)

  • Change From Baseline in Liver Iron Concentration (LIC) at 96 Weeks

    LIC was determined by R2 Magnetic Resonance Imaging (MRI).

    Baseline and 96 weeks

Secondary Outcomes (2)

  • Maximum Plasma Concentration (Cmax) of SPD602

    92 weeks

  • Area Under The Steady-state Plasma Concentration-time Curve (AUC) of SPD602

    92 weeks

Study Arms (2)

SPD602 (16mg)

EXPERIMENTAL
Drug: SPD602 (FBS0701, SSP-004184)

SPD602 (32mg)

EXPERIMENTAL
Drug: SPD602 (FBS0701, SSP-004184)

Interventions

SPD602 (FBS0701, SSP-004184)DRUG

Oral FBS0701 taken one time daily for up to 96 weeks.

SPD602 (16mg)SPD602 (32mg)

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Children's Hospital and Research Center of Oakland

Oakland, California, 94609, United States

Location

Children's Hospital of Boston

Boston, Massachusetts, 02115, United States

Location

Ospedale Regionale Microcitemie

Cagliari, Italy

Location

Centro della Microcitemia e delle Anemie Congenite

Genoa, Italy

Location

Thalassemia Center San Luigi Hospital

Orbassano, Italy

Location

Siriraj Hospital, Mahidol University

Bangkok, Thailand

Location

Pediatric Hematology, Ege University Hospital

Izmir, Turkey (Türkiye)

Location

University College London Hospital

London, United Kingdom

Location

Whittington Hospital

London, United Kingdom

Location

Related Publications (4)

  • 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: 37975597DERIVED

  • Wood JC, Zhang P, Rienhoff H, Abi-Saab W, Neufeld E. R2 and R2* are equally effective in evaluating chronic response to iron chelation. Am J Hematol. 2014 May;89(5):505-8. doi: 10.1002/ajh.23673. Epub 2014 Mar 3.

    PMID: 24452753DERIVED

  • Neufeld EJ, Galanello R, Viprakasit V, Aydinok Y, Piga A, Harmatz P, Forni GL, Shah FT, Grace RF, Porter JB, Wood JC, Peppe J, Jones A, Rienhoff HY Jr. A phase 2 study of the safety, tolerability, and pharmacodynamics of FBS0701, a novel oral iron chelator, in transfusional iron overload. Blood. 2012 Apr 5;119(14):3263-8. doi: 10.1182/blood-2011-10-386268. Epub 2012 Jan 17.

    PMID: 22251482DERIVED

  • Rienhoff HY Jr, Viprakasit V, Tay L, Harmatz P, Vichinsky E, Chirnomas D, Kwiatkowski JL, Tapper A, Kramer W, Porter JB, Neufeld EJ. A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload. Haematologica. 2011 Apr;96(4):521-5. doi: 10.3324/haematol.2010.034405. Epub 2010 Dec 20.

    PMID: 21173101DERIVED

MeSH Terms

Conditions

beta-ThalassemiaAnemia, Sickle CellIron Overload

Interventions

4,5-dihydro-2-(2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl)-4-methyl-4-thiazolecarboxylic acid

Condition Hierarchy (Ancestors)

ThalassemiaAnemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesIron Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Limitations and Caveats

Only data from all subjects (ie, total) are presented because dose adjustments that occurred after Week 24 obviated the meaningful interpretation of data presented by the original 16 and 32 mg/kg/day dose groups.

Results Point of Contact

Title
Study Director
Organization
Shire
ClinicalTransparency@shire.com
+1 866 842 5335

Study Officials

  • Study Director

    Takeda

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

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 19, 2010

First Posted

August 23, 2010

Study Start

August 13, 2010

Primary Completion

January 8, 2013

Study Completion

January 8, 2013

Last Updated

June 10, 2021

Results First Posted

June 3, 2015

Record last verified: 2021-05

Locations

US(2)GB(2)TU(1)IT(3)TH(1)