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Study for Transfusionally Iron Overloaded Children, Adolescents and Adults Using FBS0701 (SSP-004184)

Primary Purpose

Iron Overload Due to Repeated Red Blood Cell Transfusions

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SSP-004184AQ
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Iron Overload Due to Repeated Red Blood Cell Transfusions

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects and/or parents willing and able to sign the approved informed consent/and assent (based on institutional guidelines).
  • An understanding, ability, and willingness to fully comply with study procedures and restrictions.
  • Has either completed a previous SSP-004184AQ study or prematurely discontinued from (with agreement from the Investigator and Shire physician) from one of the SSP-004184AQ studies.
  • If applicable, female subjects should be either:

    1. Post-menopausal (12 consecutive months of spontaneous amenorrhea), or
    2. Surgically sterile, or
    3. Females of child-bearing potential must have a negative urine pregnancy test at the Qualification and Enrollment Visit prior to dosing on Day 1. 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.

      For subjects that did not transition directly from their feeder protocol and have initiated treatment with a chelator other than SSP-004184AQ:

  • Willing to discontinue all existing iron chelation therapies for a minimum period of 1 to 5 days prior to first dose of SSP-004184AQ.

(Note: This inclusion criterion is also applicable for subjects that were receiving chelators other than SSP-004184AQ in their feeder protocol.)

  • Serum ferritin greater than 500 ng/mL at the Qualification and Enrollment Visit.
  • Liver iron concentration (LIC) greater than or equal to 2.0 mg iron per g (equivalent dry weight, liver) determined by FerriScan® R2 MRI at the Qualification and Enrollment Visit (Day -28 to Day -8).

(Note: Younger subjects for whom MRI is not feasible will be considered iron overloaded on the basis of serum ferritin only.) - Mean of the previous 3 pre-transfusion hemoglobin concentrations greater than or equal to 7.5 g/dL.

Exclusion:

  • Unwilling to remain off all other existing chelation therapies during SSP-004184AQ dosing and for up to 24 hours from last dose.
  • A history of non-compliance in a prior FerroKin/Shire-sponsored SSP-004184AQ study (excluding dose suspensions that were medically warranted).
  • Cardiac MRI T2* less than 10.0 milliseconds at the Qualification and Enrollment Visit.
  • Cardiac left ventricular ejection fraction less than 50% at the Qualification and Enrollment Visit by MRI or below the locally determined normal range by echocardiography if MRI information is not available.
  • Evidence of clinically relevant oral, cardiovascular, gastrointestinal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow, dermatologic, hepatic, biliary, or renal dysfunction where, in the opinion of the Investigator or the Shire Study Physician, treatment with SSP-004184AQ is relatively contraindicated.
  • Platelet count below 100,000/µL or absolute neutrophil count less than 1500/mm3 at the Qualification and Enrollment Visit.
  • Known sensitivity to any ingredient in the SSP-004184AQ formulation.
  • Pregnant or lactating females.

For subjects that did not transition directly from their feeder protocol and have initiated treatment with a chelator other than SSP-004184AQ:

  • In younger subjects for whom MRI is not feasible, evidence of severe cardiac dysfunction, as assessed by the Investigator.
  • Non-elective hospitalization within the 30 days prior to receiving the first dose of SSP 004184AQ.
  • For subjects greater than or equal to 18 years old: ALT greater than 200 IU/L at the Qualification and Enrollment Visit.

OR For subjects less than 18 years old: ALT greater than 180 IU/L at the Qualification and Enrollment Visit.

- For subjects greater than or equal to 18 years old: Evidence of severe renal insufficiency, eg, serum creatinine 1.5X above the upper limit of normal or proteinuria greater than 1 gm per day or a calculated glomerular filtration rate less than 40 mL/min.

OR For subjects less than 18 years old: Evidence of significant renal insufficiency, eg, serum creatinine above the upper limit of normal or proteinuria greater than 1 gm per day.

  • Use of any investigational agent within the 30 days prior to receiving the first dose of SSP-004184AQ.
  • Cardiac left ventricular ejection fraction below the locally determined normal range in the 12 months prior to Screening by echocardiography or MRI or less than 50% at Baseline testing by MRI (Echocardiograph is acceptable for LVEF if MRI information is not available).

Sites / Locations

  • Children's Hospital Oakland
  • Children's Hospital of Boston
  • The Hospital for Sick Children
  • Toronto General Hospital
  • San Luigi Hospital Thalassemia Centre
  • Ospedale Regionale Microcitemie
  • Ospedale Galliera
  • Siriraj Hospital, Mahidol University
  • Whittington Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SSP-004814AQ

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 24 (Cycle 1)
Efficacy of SSP-004184 was assessed by determining LIC. Abdominal magnetic resonance imaging (MRI) data were collected by using FerriScan R2 standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.
Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 48 (Cycle 1)
Efficacy of SSP-004184 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. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.
Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 24 (Cycle 2)
Efficacy of SSP-004184 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. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.
Change From Baseline in Cardiac T2* Values at Week 24 (Cycle 1)
The efficacy of SSP-004184 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. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.
Change From Baseline in Cardiac T2* Values at Week 48 (Cycle 1)
The efficacy of SSP-004184 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. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.
Change From Baseline in Cardiac T2* Values at Week 24 (Cycle 2)
The efficacy of SSP-004184 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. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.

Secondary Outcome Measures

Change From Baseline in Serum Ferritin Values at Specified Visits
A negative change from baseline indicates that serum ferritin decreased. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.

Full Information

First Posted
August 16, 2012
Last Updated
June 11, 2021
Sponsor
Shire
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1. Study Identification

Unique Protocol Identification Number
NCT01671111
Brief Title
Study for Transfusionally Iron Overloaded Children, Adolescents and Adults Using FBS0701 (SSP-004184)
Official Title
A Phase 2, Open-label, Multicentre, Extension Safety and Tolerability Study for Transfusionally Iron Overloaded Children, Adolescents and Adults Using SSP-004184 (SPD602)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Why Stopped
This study was terminated due to treatment stop resulting in an inability to draw conclusions from the data. Evaluation of nonclinical rat findings is ongoing.
Study Start Date
August 14, 2012 (Actual)
Primary Completion Date
April 24, 2014 (Actual)
Study Completion Date
April 24, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire

4. Oversight

5. Study Description

Brief Summary
The purpose of this extension study is to evaluate SSP-004184AQ in patients with transfusional iron overload and to provide data on long term safety and efficacy. SSP-004184AQ is an iron chelator under development for chronic daily oral administration to patients with transfusional iron overload

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Iron Overload Due to Repeated Red Blood Cell Transfusions

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SSP-004814AQ
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
SSP-004184AQ
Other Intervention Name(s)
SPD602
Intervention Description
Long term extension study of 8-75 mg/kg/d of SSP-004184AQ (equivalent to 7-68 mg/kg/d free acid or "active" form)
Primary Outcome Measure Information:
Title
Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 24 (Cycle 1)
Description
Efficacy of SSP-004184 was assessed by determining LIC. Abdominal magnetic resonance imaging (MRI) data were collected by using FerriScan R2 standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.
Time Frame
Baseline, Week 24 (Cycle 1)
Title
Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 48 (Cycle 1)
Description
Efficacy of SSP-004184 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. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.
Time Frame
Baseline, Week 48 (Cycle 1)
Title
Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 24 (Cycle 2)
Description
Efficacy of SSP-004184 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. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.
Time Frame
Baseline, Week 24 (Cycle 2)
Title
Change From Baseline in Cardiac T2* Values at Week 24 (Cycle 1)
Description
The efficacy of SSP-004184 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. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.
Time Frame
Baseline, Week 24 (Cycle 1)
Title
Change From Baseline in Cardiac T2* Values at Week 48 (Cycle 1)
Description
The efficacy of SSP-004184 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. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.
Time Frame
Baseline, Week 48 (Cycle 1)
Title
Change From Baseline in Cardiac T2* Values at Week 24 (Cycle 2)
Description
The efficacy of SSP-004184 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. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.
Time Frame
Baseline, Week 24 (Cycle 2)
Secondary Outcome Measure Information:
Title
Change From Baseline in Serum Ferritin Values at Specified Visits
Description
A negative change from baseline indicates that serum ferritin decreased. A cycle consisted of 8 standard 6-weekly visits and the cycles were repeated each year for the duration of the study.
Time Frame
Baseline, Weeks 24 and 48 of Cycle 1, Week 24 of Cycle 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects and/or parents willing and able to sign the approved informed consent/and assent (based on institutional guidelines). An understanding, ability, and willingness to fully comply with study procedures and restrictions. Has either completed a previous SSP-004184AQ study or prematurely discontinued from (with agreement from the Investigator and Shire physician) from one of the SSP-004184AQ studies. If applicable, female subjects should be either: Post-menopausal (12 consecutive months of spontaneous amenorrhea), or Surgically sterile, or Females of child-bearing potential must have a negative urine pregnancy test at the Qualification and Enrollment Visit prior to dosing on Day 1. 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. For subjects that did not transition directly from their feeder protocol and have initiated treatment with a chelator other than SSP-004184AQ: Willing to discontinue all existing iron chelation therapies for a minimum period of 1 to 5 days prior to first dose of SSP-004184AQ. (Note: This inclusion criterion is also applicable for subjects that were receiving chelators other than SSP-004184AQ in their feeder protocol.) Serum ferritin greater than 500 ng/mL at the Qualification and Enrollment Visit. Liver iron concentration (LIC) greater than or equal to 2.0 mg iron per g (equivalent dry weight, liver) determined by FerriScan® R2 MRI at the Qualification and Enrollment Visit (Day -28 to Day -8). (Note: Younger subjects for whom MRI is not feasible will be considered iron overloaded on the basis of serum ferritin only.) - Mean of the previous 3 pre-transfusion hemoglobin concentrations greater than or equal to 7.5 g/dL. Exclusion: Unwilling to remain off all other existing chelation therapies during SSP-004184AQ dosing and for up to 24 hours from last dose. A history of non-compliance in a prior FerroKin/Shire-sponsored SSP-004184AQ study (excluding dose suspensions that were medically warranted). Cardiac MRI T2* less than 10.0 milliseconds at the Qualification and Enrollment Visit. Cardiac left ventricular ejection fraction less than 50% at the Qualification and Enrollment Visit by MRI or below the locally determined normal range by echocardiography if MRI information is not available. Evidence of clinically relevant oral, cardiovascular, gastrointestinal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow, dermatologic, hepatic, biliary, or renal dysfunction where, in the opinion of the Investigator or the Shire Study Physician, treatment with SSP-004184AQ is relatively contraindicated. Platelet count below 100,000/µL or absolute neutrophil count less than 1500/mm3 at the Qualification and Enrollment Visit. Known sensitivity to any ingredient in the SSP-004184AQ formulation. Pregnant or lactating females. For subjects that did not transition directly from their feeder protocol and have initiated treatment with a chelator other than SSP-004184AQ: In younger subjects for whom MRI is not feasible, evidence of severe cardiac dysfunction, as assessed by the Investigator. Non-elective hospitalization within the 30 days prior to receiving the first dose of SSP 004184AQ. For subjects greater than or equal to 18 years old: ALT greater than 200 IU/L at the Qualification and Enrollment Visit. OR For subjects less than 18 years old: ALT greater than 180 IU/L at the Qualification and Enrollment Visit. - For subjects greater than or equal to 18 years old: Evidence of severe renal insufficiency, eg, serum creatinine 1.5X above the upper limit of normal or proteinuria greater than 1 gm per day or a calculated glomerular filtration rate less than 40 mL/min. OR For subjects less than 18 years old: Evidence of significant renal insufficiency, eg, serum creatinine above the upper limit of normal or proteinuria greater than 1 gm per day. Use of any investigational agent within the 30 days prior to receiving the first dose of SSP-004184AQ. Cardiac left ventricular ejection fraction below the locally determined normal range in the 12 months prior to Screening by echocardiography or MRI or less than 50% at Baseline testing by MRI (Echocardiograph is acceptable for LVEF if MRI information is not available).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Children's Hospital of Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
San Luigi Hospital Thalassemia Centre
City
Orbassano
State/Province
Torino
ZIP/Postal Code
10043
Country
Italy
Facility Name
Ospedale Regionale Microcitemie
City
Cagliari
ZIP/Postal Code
09121
Country
Italy
Facility Name
Ospedale Galliera
City
Genova
ZIP/Postal Code
16128
Country
Italy
Facility Name
Siriraj Hospital, Mahidol University
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Whittington Hospital
City
London
ZIP/Postal Code
N19 5NF
Country
United Kingdom

12. IPD Sharing Statement

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Study for Transfusionally Iron Overloaded Children, Adolescents and Adults Using FBS0701 (SSP-004184)

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