Transfusional Iron OverloadPhase 2NCT01186419

Safety and Pharmacodynamic Study of an Oral Iron Chelator Given for 6 Months to Patients With Iron Overload

A Phase 2 study testing SPD602 (FBS0701, SSP-004184) in people with Transfusional Iron Overload and Beta-thalassemia, run by Shire at 9 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Transfusional Iron Overload, Beta-thalassemia
What is being tested?: SPD602 (FBS0701, SSP-004184)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 51 participants
Where: 9 sitesin 5 countries
Study dates: 13 Aug 2010to 8 Jan 2013
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

Transfusional iron overload due to: hereditary anemias such as sickle cell disease, β-thalassemia and Diamond-Blackfan anemia; acquired anemias such as Myelodysplastic Syndrome and other forms of bone marrow failure. Patients must also be transfusion-dependent and require chronic treatment with deferoxamine, deferasirox, and/or deferiprone.
Willing to discontinue all existing iron chelation therapies throughout study period.
Serum ferritin greater than 500 ng/mL at Screening.
Baseline liver iron concentration and cardiac MRI T2* per protocol requirements.
Mean of the previous three pre-transfusion hemoglobin concentrations greater than or equal to 7.5 g/dL.
Agrees to use an approved method of contraception throughout study period.

Who cannot join

As a result of medical review, physical examination or Screening investigations, the Principal Investigator considers the patient unfit for the study.
Non-elective hospitalization within the 30 days prior to Baseline testing. (Patients with sickle cell anemia who are admitted to the hospital for management of sickle crisis pain whose uncomplicated hospital course was four days or less and who, 14 days prior to Baseline testing, have returned to their previous health status are acceptable.)
Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow or skin disorder as determined by the Investigator.
Evidence of significant renal insufficiency; possible examples include: serum creatinine above the upper limit of normal, proteinuria greater than 2 gm per day or calculated creatinine clearance of less than 60 mL/minute.
Cardiac left ventricular ejection fraction outside of protocol requirements.
Known sensitivity to magnesium stearate, croscarmellose sodium or FBS0701.

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Platelet count below 100,000/µL and/or absolute neutrophil count less than 1500/mm3 at Screening and <50% at Baseline testing by MRI
Alkaline phosphatase, AST or ALT outside of protocol requirements.
Liver Function Tests: ALT >5 times the local upper limit of normal on two occasions in the previous 12 months or ALT at Screening >200 IU/L
Use of any investigational agent within the 30 days prior to the Baseline testing.

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
Centro della Microcitemia e delle Anemie Congenite
Genoa
Thalassemia Center San Luigi Hospital
Orbassano

Other trials in Italy

United States2 sites

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

Other trials in United States

United Kingdom2 sites

University College London Hospital
London
Whittington Hospital
London

Other trials in United Kingdom

Thailand1 site

Siriraj Hospital, Mahidol University
Bangkok

Other trials in Thailand

Turkey (Türkiye)1 site

Pediatric Hematology, Ege University Hospital
Izmir

Other trials in Turkey (Türkiye)

About this study

Official title: A Phase 2, 24 Week, Randomized, Open Label, Multi-Center Study to Assess the Safety, Tolerability, and Pharmacodynamics of FBS0701 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy, With a 72 Week Dosing Extension

The purpose of this research study is to evaluate the safety of two doses of FBS0701, a new oral iron chelator, and its effectiveness in clearing iron from the liver. FBS0701 is a medication taken by mouth that causes the body to get rid of iron. Iron chelators are used in patients with β-thalassemia and other forms of anemia who experience iron overload - iron increases in the body as a result of regularly required blood transfusions. Patients who qualify will be randomized to receive one of two doses of FBS0701 for up to 24 weeks (6 months) with a total study duration of up to 33 weeks. These patients will be eligible to participate in a dosing extension for up to 72 weeks. The maximum duration of dosing will be up to 96 weeks. The safety of patients will be monitored frequently during the study by physical exams, ECGs, and blood tests. To assess the amount of iron in the liver and heart, each patient must undergo 6 MRI scans during the study. Patients will not need to stay in the hospital for this study but will need to visit the outpatient clinic up to 28 times over the 96 week period. Patients currently taking an iron chelator will be required to stop for a total of up to 26 weeks. The results of this study will help to determine if FBS0701 may be effective as an iron chelator.

Conditions: Transfusional Iron Overload, Beta-thalassemia
Being tested: SPD602 (FBS0701, SSP-004184)
Keywords: Beta-thalassemia, Sickle cell anemia, Transfusional iron overload, Iron overload, Iron chelation
Medical subject headings: beta-Thalassemia, Anemia, Sickle Cell, Iron Overload

What participants receive

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

SPD602 (FBS0701, SSP-004184)Drug
Oral FBS0701 taken one time daily for up to 96 weeks.

Study groups in NCT01186419
Study group	Role	What they receive
SPD602 (16mg)	Experimental	Not described Receives: Drug: SPD602 (FBS0701, SSP-004184)
SPD602 (32mg)	Experimental	Not described Receives: Drug: SPD602 (FBS0701, SSP-004184)

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) at 96 Weeks
LIC was determined by R2 Magnetic Resonance Imaging (MRI).
Measured: Baseline and 96 weeks

Secondary outcomes (2)

Maximum Plasma Concentration (Cmax) of SPD602
Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administered.
Measured: 92 weeks
Area Under The Steady-state Plasma Concentration-time Curve (AUC) of SPD602
AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure of how much and how long a drug stays in a body.
Measured: 92 weeks

Timeline

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

13 Aug 20108 Jan 2013

First posted23 Aug 2010 (estimated)
Study start13 Aug 2010
Primary completion8 Jan 2013
Study completion8 Jan 2013

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.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Transfusional Iron OverloadStudies 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: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 51 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01186419
Sponsor's protocol ID: SPD602-201
Other IDs: 2010-019645-25, FBS0701-CTP-04
Status last verified: May 2021
First submitted: 19 Aug 2010
Last updated: 10 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Padhani ZA, Gangwani MK, Sadaf A, Hasan B, Colan S, Alvi N, Das JK. Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. Cochrane Database Syst Rev. 2023 Nov 17;11(11):CD011626. doi: 10.1002/14651858.CD011626.pub3.
PubMed 37975597
Wood JC, Zhang P, Rienhoff H, Abi-Saab W, Neufeld E. R2 and R2* are equally effective in evaluating chronic response to iron chelation. Am J Hematol. 2014 May;89(5):505-8. doi: 10.1002/ajh.23673. Epub 2014 Mar 3.
PubMed 24452753
Neufeld EJ, Galanello R, Viprakasit V, Aydinok Y, Piga A, Harmatz P, Forni GL, Shah FT, Grace RF, Porter JB, Wood JC, Peppe J, Jones A, Rienhoff HY Jr. A phase 2 study of the safety, tolerability, and pharmacodynamics of FBS0701, a novel oral iron chelator, in transfusional iron overload. Blood. 2012 Apr 5;119(14):3263-8. doi: 10.1182/blood-2011-10-386268. Epub 2012 Jan 17.
PubMed 22251482
Rienhoff HY Jr, Viprakasit V, Tay L, Harmatz P, Vichinsky E, Chirnomas D, Kwiatkowski JL, Tapper A, Kramer W, Porter JB, Neufeld EJ. A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload. Haematologica. 2011 Apr;96(4):521-5. doi: 10.3324/haematol.2010.034405. Epub 2010 Dec 20.
PubMed 21173101

Study at a glance

From the registry record, last updated by the sponsor on 10 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, 24 Week, Randomized, Open Label, Multi-Center Study to Assess the Safety, Tolerability, and Pharmacodynamics of FBS0701 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy, With a 72 Week Dosing Extension
ClinicalTrials.gov ID: NCT01186419
Acronym / sponsor ID: SPD602-201
Conditions: Transfusional Iron Overload, Beta-thalassemia
Keywords: Beta-thalassemia, Sickle cell anemia, Transfusional iron overload, Iron overload, Iron chelation
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 51 participants (actual)
Lead sponsor: ShireIndustry (pharma, biotech, devices)
Study start: 13 Aug 2010 (actual)
Primary completion: 8 Jan 2013 (actual)
Study completion: 8 Jan 2013 (actual)
First posted: 23 Aug 2010 (estimated)
Results: Posted 3 Jun 2015

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
SPD602 (16mg)	Experimental	Drug: SPD602 (FBS0701, SSP-004184)
SPD602 (32mg)	Experimental	Drug: SPD602 (FBS0701, SSP-004184)

Who may qualify

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

Key inclusion criteria (6 listed)

Transfusional iron overload due to: hereditary anemias such as sickle cell disease, β-thalassemia and Diamond-Blackfan anemia; acquired anemias such as Myelodysplastic Syndrome and other forms of bone marrow failure. Patients must also be transfusion-dependent and require chronic treatment with deferoxamine, deferasirox, and/or deferiprone.
Willing to discontinue all existing iron chelation therapies throughout study period.
Serum ferritin greater than 500 ng/mL at Screening.
Baseline liver iron concentration and cardiac MRI T2* per protocol requirements.
Mean of the previous three pre-transfusion hemoglobin concentrations greater than or equal to 7.5 g/dL.

Key exclusion criteria (10 listed)

As a result of medical review, physical examination or Screening investigations, the Principal Investigator considers the patient unfit for the study.
Non-elective hospitalization within the 30 days prior to Baseline testing. (Patients with sickle cell anemia who are admitted to the hospital for management of sickle crisis pain whose uncomplicated hospital course was four days or less and who, 14 days prior to Baseline testing, have returned to their previous health status are acceptable.)
Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow or skin disorder as determined by the Investigator.
Evidence of significant renal insufficiency; possible examples include: serum creatinine above the upper limit of normal, proteinuria greater than 2 gm per day or calculated creatinine clearance of less than 60 mL/minute.
Cardiac left ventricular ejection fraction outside of protocol requirements.

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
SPD602 (FBS0701, SSP-004184)Oral FBS0701 taken one time daily for up to 96 weeks.	Drug	SPD602 (16mg), SPD602 (32mg)

Primary outcome

Change From Baseline in Liver Iron Concentration (LIC) at 96 Weeks
Time frame: Baseline and 96 weeks
LIC was determined by R2 Magnetic Resonance Imaging (MRI).

2 secondary outcomes

Maximum Plasma Concentration (Cmax) of SPD602
Time frame: 92 weeks
Area Under The Steady-state Plasma Concentration-time Curve (AUC) of SPD602
Time frame: 92 weeks

Results and safety

Results posted to the registry on 3 Jun 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 16 mg/kg/Day	24	17
SPD602 32 mg/kg/Day	27	18

Primary outcome: Change From Baseline in Liver Iron Concentration (LIC) at 96 Weeks

Time frame: Baseline and 96 weeks. Mean (Standard Deviation). Unit: mg/g

Measure	SPD602 n = 26
Value	-1.75 (4.839)

SPD602: p = 0.0765, t-test, 2 sided

Population analysed: Full Analysis Set, defined as all subjects in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all subjects who received any amount of investigational product.

2 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 16 mg/kg/d	3 of 24 (12.5%)	24 of 24 (100%)	Not reported
SPD602 32 mg/kg/d	2 of 27 (7.4%)	26 of 27 (96.3%)	Not reported

Limitations and caveats (from the sponsor): Only data from all subjects (ie, total) are presented because dose adjustments that occurred after Week 24 obviated the meaningful interpretation of data presented by the original 16 and 32 mg/kg/day dose groups.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37975597Padhani ZA, Gangwani MK, Sadaf A, Hasan B, Colan S, Alvi N, Das JK. Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. Cochrane Database Syst Rev. 2023 Nov 17;11(11):CD011626. doi: 10.1002/14651858.CD011626.pub3.
Derived from this study: PubMed 24452753Wood JC, Zhang P, Rienhoff H, Abi-Saab W, Neufeld E. R2 and R2* are equally effective in evaluating chronic response to iron chelation. Am J Hematol. 2014 May;89(5):505-8. doi: 10.1002/ajh.23673. Epub 2014 Mar 3.
Derived from this study: PubMed 22251482Neufeld EJ, Galanello R, Viprakasit V, Aydinok Y, Piga A, Harmatz P, Forni GL, Shah FT, Grace RF, Porter JB, Wood JC, Peppe J, Jones A, Rienhoff HY Jr. A phase 2 study of the safety, tolerability, and pharmacodynamics of FBS0701, a novel oral iron chelator, in transfusional iron overload. Blood. 2012 Apr 5;119(14):3263-8. doi: 10.1182/blood-2011-10-386268. Epub 2012 Jan 17.
Derived from this study: PubMed 21173101Rienhoff HY Jr, Viprakasit V, Tay L, Harmatz P, Vichinsky E, Chirnomas D, Kwiatkowski JL, Tapper A, Kramer W, Porter JB, Neufeld EJ. A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload. Haematologica. 2011 Apr;96(4):521-5. doi: 10.3324/haematol.2010.034405. Epub 2010 Dec 20.

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 SPD602 (FBS0701, SSP-004184) in people with Transfusional Iron Overload and Beta-thalassemia, 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 6 inclusion and 10 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: finished, as of the sponsor's last update on 10 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, United Kingdom, Thailand, Turkey (Türkiye). 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 3 Jun 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) at 96 Weeks (time frame: Baseline and 96 weeks). 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 NCT01186419, which also lists 4 linked publications.

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 10 Jun 2021.