Safety, Efficacy and Pharmacokinetics of an Oral Iron Chelator Given for a Year to Pediatric Patients With Iron Overload

June 10, 2021 updated by: Shire

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada
        • Toronto Sick Kids Hospital
  • Italy
      • Cagliari, Italy, 09121
        • Ospedale Regionale Mecrocitemie
      • Genoa, Italy
        • Centro della Microcitemia e delle Anemie Congenite
      • Orbassano, Italy
        • Thalassemia Center San Luigi Hospital
  • Lebanon
      • Beirut, Lebanon
        • American University of Beirut Medical Center
      • Beirut, Lebanon
        • Chronic Care Center
  • Turkey
      • Izmir, Turkey, 35100
        • Ege University Hospital
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital Boston
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: SPD602 (26 mg/kg)
Oral SSP-004184AQ taken once daily for 48 weeks
Drug: SPD602
Other Names:
  • SSP-004184, deferitazole
Experimental: SPD602 (36 mg/kg)
Oral SSP-004184AQ taken once daily for 48 weeks. Starting dose based on transfusion burden and iron overload status. Doses may range from 8-60mg/kg/day depending on clinical response.
Drug: SPD602
Other Names:
  • SSP-004184, deferitazole
Experimental: SPD602 (16 mg/kg)
A single dose given in the initial pharmacokinetic phase.
Drug: SPD602
Other Names:
  • SSP-004184, deferitazole

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Observed Plasma Concentration (Cmax) of SPD602 After a Single Oral Dose
Time Frame: Day 1 and up to 24 hours post-dose
The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis.
Day 1 and up to 24 hours post-dose
Time of Maximum Observed Plasma Concentration Sampled During a Dosing Interval (Tmax) of SPD602 After a Single Oral Dose
Time Frame: Day 1 and up to 24 hours post-dose
The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis.
Day 1 and up to 24 hours post-dose
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
Time Frame: Day 1 and up to 24 hours post-dose
The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis.
Day 1 and up to 24 hours post-dose
Terminal Half-life (t1/2) of SPD602 After a Single Oral Dose
Time Frame: Day 1 and up to 24 hours post-dose
The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis.
Day 1 and up to 24 hours post-dose
Renal Clearance (CLr) of SPD602 After a Single Oral Dose
Time Frame: Day 1 and up to 24 hours post-dose
The pharmacokinetic (PK) parameters of SPD602 were measured in urine of patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. Children who could cooperate provided urine samples for PK assessment on Day 1 over 3 time intervals: 0-4, 4-8, and 8-24 hours after the last dose (continued into Day 2). Urine concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from urine concentration-time data for SPD602 (total) by non-compartmental analysis.
Day 1 and up to 24 hours post-dose
Amount Excreted Into Urine (Ue) of SPD602 After a Single Oral Dose
Time Frame: Day 1 and up to 24 hours post-dose
The pharmacokinetic (PK) parameters of SPD602 were measured in urine of patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. Children who could cooperate provided urine samples for PK assessment on Day 1 over 3 time intervals: 0-4, 4-8, and 8-24 hours after the last dose (continued into Day 2). Urine concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from urine concentration-time data for SPD602 (total) by non-compartmental analysis.
Day 1 and up to 24 hours post-dose
Fraction Of Orally Administered Drug Excreted Unchanged In Urine (fe) of SPD602 After a Single Oral Dose
Time Frame: Day 1 and up to 24 hours post-dose
The pharmacokinetic (PK) parameters of SPD602 were measured in urine of patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. Children who could cooperate provided urine samples for PK assessment on Day 1 over 3 time intervals: 0-4, 4-8, and 8-24 hours after the last dose (continued into Day 2). Urine concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from urine concentration-time data for SPD602 (total) by non-compartmental analysis.
Day 1 and up to 24 hours post-dose
Change From Baseline in Liver Iron Concentration (LIC) Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)
Time Frame: Baseline, 24 weeks, and 48 weeks
The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using FerriScan R2 standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased.
Baseline, 24 weeks, and 48 weeks
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI
Time Frame: Baseline, 24 weeks, and 48 weeks
The efficacy of SPD602 was assessed by determining LIC and adjusting for transfusional iron intake. Abdominal MRI data were collected by using FerriScan R2 standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased.
Baseline, 24 weeks, and 48 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in LIC Assessed by R2* MRI
Time Frame: Baseline, 24 weeks, and 48 weeks
The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using R2* standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased.
Baseline, 24 weeks, and 48 weeks
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI
Time Frame: Baseline, 24 weeks, and 48 weeks
The efficacy of SPD602 was assessed by determining LIC and adjusting for transfusional iron intake. Abdominal MRI data were collected by using R2* standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased.
Baseline, 24 weeks, and 48 weeks
Change From Baseline in Cardiac Iron Load Assessed by T2* MRI
Time Frame: Baseline, 24 weeks, and 48 weeks
The efficacy of SPD602 was assessed by determining cardiac iron load. Cardiac MRI data were collected by using T2* standard procedures and used to determine iron load. A negative change from baseline indicates that iron load increased.
Baseline, 24 weeks, and 48 weeks
Change From Baseline in Serum Ferritin
Time Frame: Baseline, 24 weeks, and 48 weeks
Serum ferritin levels were assessed to determine if a participant was a successful responder and were determined from serum biochemistry analyses conducted at the central laboratories. A negative change from baseline indicates that serum ferritin decreased.
Baseline, 24 weeks, and 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shire

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 10, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 13, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 13, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 30, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 31, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 2, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 14, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 10, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SPD602-202
  • SSP-004184AQ (Other Identifier: Shire)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings