Clinical trial NCT01186419: Safety and Pharmacodynamic Study of an Oral Iron Chelator Given for 6 Months to Patients With Iron Overload
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Transfusional Iron Overload
Beta-thalassemia
Keywords: Beta-thalassemia
Sickle cell anemia
Transfusional iron overload
Iron overload
Iron chelation
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-08-23
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change From Baseline in Liver Iron Concentration (LIC) at 96 Weeks
timeFrame: Baseline and 96 weeks
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of SPD602
timeFrame: 92 weeks
measure: Area Under The Steady-state Plasma Concentration-time Curve (AUC) of SPD602
timeFrame: 92 weeks
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital and Research Center of Oakland
state: California
city: Boston
country: United States
facility: Children's Hospital of Boston
state: Massachusetts
city: Cagliari
country: Italy
facility: Ospedale Regionale Microcitemie
city: Genoa
country: Italy
facility: Centro della Microcitemia e delle Anemie Congenite
city: Orbassano
country: Italy
facility: Thalassemia Center San Luigi Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital, Mahidol University
city: Izmir
country: Turkey
facility: Pediatric Hematology, Ege University Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: Whittington Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.