Clinical trial NCT01363908: Safety, Efficacy and Pharmacokinetics of an Oral Iron Chelator Given for a Year to Pediatric Patients With Iron Overload
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
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: 2011-06-02
Enrollment: 30
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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 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).

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of SPD602 After a Single Oral Dose
timeFrame: Day 1 and up to 24 hours post-dose
measure: Time of Maximum Observed Plasma Concentration Sampled During a Dosing Interval (Tmax) of SPD602 After a Single Oral Dose
timeFrame: Day 1 and up to 24 hours post-dose
measure: Area Under The Plasma Concentration-Time Curve (AUC) From The Time of Dosing to The Last Measurable Concentration (AUClast) of SPD602 After a Single Oral Dose
timeFrame: Day 1 and up to 24 hours post-dose
measure: Terminal Half-life (t1/2) of SPD602 After a Single Oral Dose
timeFrame: Day 1 and up to 24 hours post-dose
measure: Renal Clearance (CLr) of SPD602 After a Single Oral Dose
timeFrame: Day 1 and up to 24 hours post-dose
measure: Amount Excreted Into Urine (Ue) of SPD602 After a Single Oral Dose
timeFrame: Day 1 and up to 24 hours post-dose
measure: Fraction Of Orally Administered Drug Excreted Unchanged In Urine (fe) of SPD602 After a Single Oral Dose
timeFrame: Day 1 and up to 24 hours post-dose
measure: Change From Baseline in Liver Iron Concentration (LIC) Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, 24 weeks, and 48 weeks
measure: Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI
timeFrame: Baseline, 24 weeks, and 48 weeks
Secondary outcomes:
measure: Change From Baseline in LIC Assessed by R2* MRI
timeFrame: Baseline, 24 weeks, and 48 weeks
measure: Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI
timeFrame: Baseline, 24 weeks, and 48 weeks
measure: Change From Baseline in Cardiac Iron Load Assessed by T2* MRI
timeFrame: Baseline, 24 weeks, and 48 weeks
measure: Change From Baseline in Serum Ferritin
timeFrame: Baseline, 24 weeks, and 48 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Toronto
country: Canada
facility: Toronto Sick Kids Hospital
state: Ontario
city: Cagliari
country: Italy
facility: Ospedale Regionale Mecrocitemie
city: Genoa
country: Italy
facility: Centro della Microcitemia e delle Anemie Congenite
city: Orbassano
country: Italy
facility: Thalassemia Center San Luigi Hospital
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
city: Beirut
country: Lebanon
facility: Chronic Care Center
city: Izmir
country: Turkey
facility: Ege University Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: