Iron Overload Due to Repeated Red Blood Cell TransfusionsPhase 2NCT01604941

Pharmacokinetics of SSP-004184 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy

A Phase 2 study testing SPD602 in people with Iron Overload Due to Repeated Red Blood Cell Transfusions, run by Shire at 12 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 study is to evaluate SSP-004184AQ in patients with transfusional iron overload whose primary diagnosis is hereditary or congenital anemia. 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 18 to 60 years
Conditions the study is for: Iron Overload Due to Repeated Red Blood Cell Transfusions
What is being tested?: SPD602
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 12 sitesin 5 countries
Study dates: 14 Sep 2012to 18 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 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Willing and able to sign the approved informed consent.
Age: 18-60 years old, inclusive, at Screening.
Subjects who have received more than 20 transfusions in their lifetime and who have transfusional iron overload requiring chronic treatment with an iron chelator. N.B.: Sickle Cell Disease subjects receiving regular exchange transfusions and iron overloaded subjects with thalassemia intermedia who are receiving regular transfusions (transfusion dependent thalassemia intermedia) are eligible.
Willing to discontinue all existing iron chelation therapies for a minimum period of one to five days prior to first dose of SSP-004184AQ, the 24 week duration of the study and 1 week after last dose for a total of approximately 26 weeks.
Willing to fast two hours prior to and one hour after each dose.
Serum ferritin >500ng/mL at Screening.

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Baseline liver iron concentration is greater than or equal to 5mg iron per g (equivalent dry weight, liver)determined by FerriScan® R2 MRI.
Mean of the previous three pre-transfusion hemoglobin concentrations is greater than or equal to 7.5g/dL.
Adult female subjects should be:
Post-menopausal (12 consecutive months of spontaneous amenorrhea), or
Surgically sterile, or
Females of child-bearing potential must have a negative 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.

Who cannot join

As a result of medical review, physical examination, or Screening investigations, the Principal Investigator (PI) considers the subject unfit for the study.
Non-elective hospitalization within the 30 days prior to Baseline testing.
Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, biliary, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow, or skin disorder that contraindicates dosing with SSP-004184AQ.
Iron overload from causes other than transfusional siderosis.
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 <60mL/min.
Severe iron overload including:

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T2* MRI <10 ms
liver iron concentration by FerriScan R2 MRI >30mg/g liver (dw)
Known sensitivity to magnesium stearate, croscarmellose sodium or SSP-004184AQ.
Platelet count below 100,000/μL or absolute neutrophil count less than 1500/mm3 at Screening.
Insufficient venous access that precludes prescribed blood draws for safety laboratory assessments.
ALT at Screening >200 IU/L.
Use of any investigational agent within the 30 days prior to the Baseline testing.
Pregnant or lactating females.
Cardiac left ventricular ejection fraction
Below the locally determined normal range in the 12 months prior to Screening by echocardiograph or MRI or
<50% at Baseline testing by MRI (echocardiograph is acceptable for LVEF if MRI information is not available).

Trial locations and contacts

12 sites in 5 countries.

Country

City, postcode or hospital

12 sites in 5 countries

United States4 sites

Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Children's Center for Cancer and Blood Diseases
Los Angeles, California, 90027
Weill Cornell Medical College
New York, New York, 10065
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104

Other trials in United States

Italy4 sites

Ospedale Regionale Microcitemie
Cagliari, 09121
Centro della Microcitemia e delle Anemie Congenite
Genova, Genoa, 16128
Ospedale Maggiore Policlinico
Milan, 20122
San Luigi Hospital Thalassemia Centre
Orbassano, Torino, 10043

Other trials in Italy

Egypt2 sites

Ain Shams University Pediatric Hospitals
Cairo
Cairo University Pediatric Hospitals
Cairo

Other trials in Egypt

Canada1 site

Toronto General Hospital
Toronto, Ontario, M5G 2C4

Other trials in Canada

Lebanon1 site

American University of Beirut Medical Center
Beirut

Other trials in Lebanon

About this study

Official title: A Phase 2, 24 Week, Open Label, Multi-Center Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SSP-004184 (SPD602) in the Treatment of Chronic Iron Overload Requiring Chelation Therapy

The purpose of this study is to evaluate SSP-004184AQ in patients with transfusional iron overload whose primary diagnosis is hereditary or congenital anemia.

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: SPD602

What participants receive

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

SPD602Drug
Also called SSP-004184, deferitazole
50 mg/kg/day orally twice daily for 24 weeks

Study groups in NCT01604941
Study group	Role	What they receive
SPD602	Experimental	50 mg/kg/day orally twice daily for 24 weeks Receives: Drug: SPD602

What is being measured

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

Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)
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. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Measured: Baseline, 12 and 24 weeks
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI
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. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Measured: Baseline, 12 and 24 weeks

Secondary outcomes (9)

Change From Baseline in LIC as Assessed by R2* MRI
The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using R2* standard procedures (liver and pancreas) and used to determine LIC. A negative change from baseline indicates that LIC decreased. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Measured: Baseline, 12 and 24 weeks
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI
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 (liver and pancreas) and used to determine LIC. A negative change from baseline indicates that LIC decreased. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Measured: Baseline, 12 and 24 weeks
Change From Baseline in Cardiac T2* Relaxation Rate, an MRI Parameter Used to Estimate Cardiac Iron Load
The efficacy of SPD602 was assessed by estimating cardiac iron load. T2* data from cardiac MRI were collected by using standard procedures and used as an estimate of cardiac iron load. T2* is an MR relaxation parameter that is reported in milliseconds. Iron within a tissue decreases homogeneity of the magnetic field and shortens the T2* relaxation rate (Anderson, 2001). Low cardiac T2* values are associated with increased risk of heart failure (Kirk, 2009). A negative change from baseline in the T2* relaxation rate indicates that iron load increased. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Measured: Baseline, 12 and 24 weeks
Change From Baseline in Serum Ferritin
Serum ferritin levels were determined from serum biochemistry analyses. A negative change from baseline indicates that serum ferritin decreased.
Measured: Baseline, 8 and 16 weeks
Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC
A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value. LIC was assessed by abdominal MRI with the FerriScan R2 according to standard procedures. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Measured: 12 and 24 weeks
Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC Adjusted For Transfusional Iron Intake
A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value. LIC was assessed by abdominal MRI with the FerriScan R2 according to standard procedures, and the results were adjusted for transfusional iron intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake.
Measured: 12 and 24 weeks
Number of Participants Classified as a Responder by R2* MRI Analysis of LIC
A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value. LIC was assessed by abdominal MRI with the R2* according to standard procedures (liver and pancreas). Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Measured: 12 and 24 weeks
Number of Participants Classified as a Responder by R2* MRI Analysis of LIC Adjusted For Transfusional Iron Intake
A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value. LIC was assessed by abdominal MRI with the R2* according to standard procedures (liver and pancreas), and the results were adjusted for transfusional iron intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake.
Measured: 12 and 24 weeks
Number of Participants Classified as a Responder by Serum Ferritin
A responder was defined as a participant whose observed serum ferritin level at the measured time point was less than the baseline value. Serum ferritin levels were determined from serum biochemistry analyses.
Measured: 8 and 16 weeks

Timeline

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

14 Sep 201218 Apr 2014

First posted24 May 2012 (estimated)
Study start14 Sep 2012
Primary completion18 Apr 2014
Study completion18 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: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01604941
Sponsor's protocol ID: SPD602-203
Other IDs: FBS0701-CTP-16, 2011-005675-16
Status last verified: Jun 2021
First submitted: 22 May 2012
Last updated: 29 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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, 24 Week, Open Label, Multi-Center Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SSP-004184 (SPD602) in the Treatment of Chronic Iron Overload Requiring Chelation Therapy
ClinicalTrials.gov ID: NCT01604941
Acronym / sponsor ID: SPD602-203
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: 32 participants (actual)
Lead sponsor: ShireIndustry (pharma, biotech, devices)
Study start: 14 Sep 2012 (actual)
Primary completion: 18 Apr 2014 (actual)
Study completion: 18 Apr 2014 (actual)
First posted: 24 May 2012 (estimated)
Results: Posted 17 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 study is to evaluate SSP-004184AQ in patients with transfusional iron overload whose primary diagnosis is hereditary or congenital anemia.

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
SPD602	Experimental	Drug: SPD60250 mg/kg/day orally twice daily for 24 weeks

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (13 listed)

Willing and able to sign the approved informed consent.
Age: 18-60 years old, inclusive, at Screening.
Subjects who have received more than 20 transfusions in their lifetime and who have transfusional iron overload requiring chronic treatment with an iron chelator. N.B.: Sickle Cell Disease subjects receiving regular exchange transfusions and iron overloaded subjects with thalassemia intermedia who are receiving regular transfusions (transfusion dependent thalassemia intermedia) are eligible.
Willing to discontinue all existing iron chelation therapies for a minimum period of one to five days prior to first dose of SSP-004184AQ, the 24 week duration of the study and 1 week after last dose for a total of approximately 26 weeks.
Willing to fast two hours prior to and one hour after each dose.

Key exclusion criteria (17 listed)

As a result of medical review, physical examination, or Screening investigations, the Principal Investigator (PI) considers the subject unfit for the study.
Non-elective hospitalization within the 30 days prior to Baseline testing.
Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, biliary, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow, or skin disorder that contraindicates dosing with SSP-004184AQ.
Iron overload from causes other than transfusional siderosis.
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 <60mL/min.

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
SPD602Also: SSP-004184, deferitazole50 mg/kg/day orally twice daily for 24 weeks	Drug	SPD602

Primary outcome

Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)
Time frame: Baseline, 12 and 24 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. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI
Time frame: Baseline, 12 and 24 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. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.

9 secondary outcomes

Change From Baseline in LIC as Assessed by R2* MRI
Time frame: Baseline, 12 and 24 weeks
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI
Time frame: Baseline, 12 and 24 weeks
Change From Baseline in Cardiac T2* Relaxation Rate, an MRI Parameter Used to Estimate Cardiac Iron Load
Time frame: Baseline, 12 and 24 weeks
Change From Baseline in Serum Ferritin
Time frame: Baseline, 8 and 16 weeks
Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC
Time frame: 12 and 24 weeks
Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC Adjusted For Transfusional Iron Intake
Time frame: 12 and 24 weeks
Number of Participants Classified as a Responder by R2* MRI Analysis of LIC
Time frame: 12 and 24 weeks
Number of Participants Classified as a Responder by R2* MRI Analysis of LIC Adjusted For Transfusional Iron Intake
Time frame: 12 and 24 weeks
Number of Participants Classified as a Responder by Serum Ferritin
Time frame: 8 and 16 weeks

Results and safety

Results posted to the registry on 17 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
SPD602 50mg/mg/Day Twice Daily Dosing (BID)	11	0
SPD602 75mg/kg/Day Twice Daily Dosing (BID)	4	0
SPD602 50mg/kg/Day Once (QD) Then Twice Daily Dosing (BID)	3	0
SPD602 75mg/kg/Day Once (QD) Then Twice Daily Dosing (BID)	3	0
SPD602 50mg/kg/Day Once Daily Dosing (QD)	4	3
SPD602 75mg/kg/Day Once Daily Dosing (QD)	7	0

Primary outcome: Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)

Time frame: Baseline, 12 and 24 weeks. Mean (Standard Deviation). Unit: mg Fe/g*dw

Measure	SPD602 50 mg/kg/d n = 5	All Participants With BID Dosing n = 11
Week 12, n=5,10	-3.4 (6.4)	-3.8 (5.0)
Week 24, n=1,2	-5.3 (NA)	-2.1 (4.5)

SPD602 50 mg/kg/d: p = 0.2960, paired t-test
All Participants With BID Dosing: p = 0.0400, paired t-test
All Participants With BID Dosing: p = 0.6303, paired t-test

Population analysed: The Full Analysis Set, defined as all participants in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all participants who had taken at least 1 BID dose of investigational product.

Primary outcome: Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI

Time frame: Baseline, 12 and 24 weeks. Mean (Standard Deviation). Unit: mg Fe/g*dw

Measure	SPD602 50 mg/kg/d n = 5	All Participants With BID Dosing n = 11
Week 12, n=5,10	-6.3 (8.4)	-6.6 (6.7)
Week 24, n=1,2	-12.8 (NA)	-9.3 (5.0)

SPD602 50 mg/kg/d: p = 0.1683, paired t-test
All Participants With BID Dosing: p = 0.0123, paired t-test
All Participants With BID Dosing: p = 0.2334, paired t-test

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
SPD602 50mg/kg/Day	2 of 12 (16.7%)	9 of 12 (75%)	Not reported
SPD602 75mg/kg/Day	2 of 7 (28.6%)	7 of 7 (100%)	Not reported

Limitations and caveats (from the sponsor): 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.

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

12 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 SPD602 in people with Iron Overload Due to Repeated Red Blood Cell Transfusions, run by Shire at 12 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 12 sites in United States, Italy, Egypt, Canada, Lebanon. 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 17 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 Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI) (time frame: Baseline, 12 and 24 weeks). The study lists 2 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 NCT01604941.

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.