Iron Overload Due to Repeated Red Blood Cell TransfusionsPhase 2NCT01671111

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

A Phase 2 study testing SSP-004184AQ in people with Iron Overload Due to Repeated Red Blood Cell Transfusions, run by Shire at 9 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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 Read more about this study

Who is it for?: Ages 6 years and older
Conditions the study is for: Iron Overload Due to Repeated Red Blood Cell Transfusions
What is being tested?: SSP-004184AQ
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 9 sitesin 5 countries
Study dates: 14 Aug 2012to 24 Apr 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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

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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.

Who cannot join

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.

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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).

Trial locations and contacts

9 sites in 5 countries.

Country

City, postcode or hospital

9 sites in 5 countries

Italy3 sites

Ospedale Regionale Microcitemie
Cagliari, 09121
Ospedale Galliera
Genova, 16128
San Luigi Hospital Thalassemia Centre
Orbassano, Torino, 10043

Other trials in Italy

United States2 sites

Children's Hospital of Boston
Boston, Massachusetts, 02115
Children's Hospital Oakland
Oakland, California, 94609

Other trials in United States

Canada2 sites

The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Toronto General Hospital
Toronto, Ontario, M5G 2C4

Other trials in Canada

Thailand1 site

Siriraj Hospital, Mahidol University
Bangkok, 10700

Other trials in Thailand

United Kingdom1 site

Whittington Hospital
London, N19 5NF

Other trials in United Kingdom

About this study

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)

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

Conditions: Iron Overload Due to Repeated Red Blood Cell Transfusions
Being tested: SSP-004184AQ

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SSP-004184AQDrug
Also called SPD602
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)

Study groups in NCT01671111
Study group	Role	What they receive
SSP-004814AQ	Experimental	Not described Receives: Drug: SSP-004184AQ

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, Week 24 (Cycle 1)
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.
Measured: Baseline, Week 48 (Cycle 1)
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.
Measured: Baseline, Week 24 (Cycle 2)
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.
Measured: Baseline, Week 24 (Cycle 1)
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.
Measured: Baseline, Week 48 (Cycle 1)
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.
Measured: Baseline, Week 24 (Cycle 2)

Secondary outcomes (1)

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.
Measured: Baseline, Weeks 24 and 48 of Cycle 1, Week 24 of Cycle 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Aug 201224 Apr 2014

First posted23 Aug 2012 (estimated)
Study start14 Aug 2012
Primary completion24 Apr 2014
Study completion24 Apr 2014

Why it 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.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Iron Overload Due to Repeated Red Blood Cell TransfusionsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01671111
Sponsor's protocol ID: SPD602-301
Other IDs: 2011-006322-25
Status last verified: Jun 2021
First submitted: 16 Aug 2012
Last updated: 29 Jun 2021
Results posted: Yes, on ClinicalTrials.gov

Study at a glance

From the registry record, last updated by the sponsor on 29 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT01671111
Acronym / sponsor ID: SPD602-301
Conditions: Iron Overload Due to Repeated Red Blood Cell Transfusions
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason 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.
Enrolment: 30 participants (actual)
Lead sponsor: ShireIndustry (pharma, biotech, devices)
Study start: 14 Aug 2012 (actual)
Primary completion: 24 Apr 2014 (actual)
Study completion: 24 Apr 2014 (actual)
First posted: 23 Aug 2012 (estimated)
Results: Posted 6 Aug 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
SSP-004814AQ	Experimental	Drug: SSP-004184AQ

Who may qualify

Ages: 6 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (13 listed)

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

Key exclusion criteria (17 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SSP-004184AQAlso: SPD602Long term extension study of 8-75 mg/kg/d of SSP-004184AQ (equivalent to 7-68 mg/kg/d free acid or "active" form)	Drug	SSP-004814AQ

Primary outcome

Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 24 (Cycle 1)
Time frame: Baseline, 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)
Time frame: Baseline, 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)
Time frame: Baseline, 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)
Time frame: Baseline, 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)
Time frame: Baseline, 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)
Time frame: Baseline, 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.

1 secondary outcome

Change From Baseline in Serum Ferritin Values at Specified Visits
Time frame: Baseline, Weeks 24 and 48 of Cycle 1, Week 24 of Cycle 2

Results and safety

Results posted to the registry on 6 Aug 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
SSP-004184AQ	30	0

Primary outcome: Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 24 (Cycle 1)

Time frame: Baseline, Week 24 (Cycle 1). Mean (Standard Deviation). Unit: milligram per gram (mg/g) dry tissue

Measure	SSP-004184AQ n = 23
Baseline (n=23)	9.9 (8.10)
Change at Week 24 (Cycle 1) (n=13)	-1.1 (1.86)

SSP-004184AQ: p = 0.0560, paired t-test

Population analysed: Full analysis set (FAS) included all participants in the Safety set who had at least 1 post-baseline primary efficacy assessment. Here, 'n' signifies the number of FAS participants evaluable for the respective time points.

Primary outcome: Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 48 (Cycle 1)

Time frame: Baseline, Week 48 (Cycle 1). Mean (Standard Deviation). Unit: mg/g dry tissue

Measure	SSP-004184AQ n = 9
Value	-1.0 (1.68)

SSP-004184AQ: p = 0.1232, paired t-test

Population analysed: FAS participants evaluable for this outcome.

Primary outcome: Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 24 (Cycle 2)

Time frame: Baseline, Week 24 (Cycle 2). Mean (Standard Deviation). Unit: mg/g dry tissue

Measure	SSP-004184AQ n = 7
Value	-1.5 (2.23)

SSP-004184AQ: p = 0.1319, paired t-test

Population analysed: FAS participants evaluable for this outcome.

Primary outcome: Change From Baseline in Cardiac T2* Values at Week 24 (Cycle 1)

Time frame: Baseline, Week 24 (Cycle 1). Mean (Standard Deviation). Unit: milliseconds

Measure	SSP-004184AQ n = 23
Baseline (n=23)	35.14 (12.242)
Change at Week 24 (Cycle 1) (n=14)	-0.41 (8.069)

SSP-004184AQ: p = 0.8061, paired t-test

Population analysed: FAS. Here, 'n' signifies the number of FAS participants evaluable for the respective time points.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From start of study treatment up to the end of study (1 week after the end of treatment). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
SSP-004184AQ	2 of 30 (6.7%)	25 of 30 (83.3%)	Not reported

Limitations and caveats (from the sponsor): This study was terminated early due to non-clinical safety results. Not all participants completed the study. The available efficacy data were analyzed as specified in the statistical analysis plan; however, no efficacy conclusions were drawn.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Study Director study director

Takeda

9 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SSP-004184AQ in people with Iron Overload Due to Repeated Red Blood Cell Transfusions, run by Shire at 9 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Italy, United States, Canada, Thailand, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 24 (Cycle 1) (time frame: Baseline, Week 24 (Cycle 1)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01671111.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2021; AzTrials last refreshed its copy on 6 Nov 2026.