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

• Sponsor: Shire (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01671111
• Collaborator: (none)
• Enrollment: 30
• Locations: 9
• Arm: 1
• Actual Duration (Months): 20.3
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.2

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Iron Overload Due to Repeated Red Blood Cell Transfusions	Drug: SSP-004184AQ	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Aug 14, 2012
• Actual Primary Completion Date: Apr 24, 2014
• Actual Study Completion Date: Apr 24, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SSP-004814AQ	Drug: SSP-004184AQ; 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); Other Names: SPD602

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 24 (Cycle 1) [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.

2. Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 48 (Cycle 1) [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.

3. Change From Baseline in Ferriscan® R2 Liver Iron Concentrations (LIC) at Week 24 (Cycle 2) [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.

4. Change From Baseline in Cardiac T2* Values at Week 24 (Cycle 1) [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.

5. Change From Baseline in Cardiac T2* Values at Week 48 (Cycle 1) [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.

6. Change From Baseline in Cardiac T2* Values at Week 24 (Cycle 2) [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.

Secondary Outcome Measures

1. Change From Baseline in Serum Ferritin Values at Specified Visits [Baseline, Weeks 24 and 48 of Cycle 1, Week 24 of Cycle 2]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Oakland	Oakland	California	United States	94609
2	Children's Hospital of Boston	Boston	Massachusetts	United States	02115
3	The Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
4	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
5	San Luigi Hospital Thalassemia Centre	Orbassano	Torino	Italy	10043
6	Ospedale Regionale Microcitemie	Cagliari		Italy	09121
7	Ospedale Galliera	Genova		Italy	16128
8	Siriraj Hospital, Mahidol University	Bangkok		Thailand	10700
9	Whittington Hospital	London		United Kingdom	N19 5NF

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01671111
• Other Study ID Numbers: SPD602-301; 2011-006322-25
• First Posted: Aug 23, 2012
• Last Update Posted: Jun 29, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Iron Overload

Study Results

Participant Flow

Pre-assignment Detail	A total of 30 participants were enrolled to this open-label extension study (24 participants transferred directly from feeder studies SPD602-201 [NCT01186419], SPD602-202 [NCT01363908], and SPD602-203 [NCT01604941] and 6 participants did not transfer directly and received a chelator other than SSP-004184 after discontinuation from a feeder study).

Arm/Group Title	SSP-004184AQ
Arm/Group Description	Participants received SSP-004184AQ (magnesium salt of free acid or active form, that is, SSP-004184 [SPD602, FBS0701]) capsules orally at a total daily dose of 8-75 milligram per kilogram per day (mg/kg/day) (equivalent to SSP-004184 7-68 mg/kg/day) either once daily or twice daily at the discretion of investigator for up to a maximum of 3 years or until the sponsor decided to stop the study.
Period Title: Overall Study
STARTED	30
COMPLETED	0
NOT COMPLETED	30

Baseline Characteristics

Arm/Group Title	SSP-004184AQ
Arm/Group Description	Participants received SSP-004184AQ (magnesium salt of free acid or active form, that is, SSP-004184 [SPD602, FBS0701]) capsules orally at a total daily dose of 8-75 mg/kg/day (equivalent to SSP-004184 7-68 mg/kg/day) either once daily or twice daily at the discretion of investigator for up to a maximum of 3 years or until the sponsor decided to stop the study.
Overall Participants	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.5 (11.38)
Sex: Female, Male (Count of Participants)
Female	17 56.7%
Male	13 43.3%

Outcome Measures

1. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	SSP-004184AQ
Arm/Group Description	Participants received SSP-004184AQ (magnesium salt of free acid or active form, that is, SSP-004184 [SPD602, FBS0701]) capsules orally at a total daily dose of 8-75 mg/kg/day (equivalent to SSP-004184 7-68 mg/kg/day) either once daily or twice daily at the discretion of investigator for up to a maximum of 3 years or until the sponsor decided to stop the study.
Measure Participants	23
Baseline (n=23)	9.9 (8.10)
Change at Week 24 (Cycle 1) (n=13)	-1.1 (1.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SSP-004184AQ
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0560
	Comments	P-value was from paired t-test for post treatment timepoint versus baseline.
	Method	paired t-test
	Comments

2. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

FAS participants evaluable for this outcome.

Arm/Group Title	SSP-004184AQ
Arm/Group Description	Participants received SSP-004184AQ (magnesium salt of free acid or active form, that is, SSP-004184 [SPD602, FBS0701]) capsules orally at a total daily dose of 8-75 mg/kg/day (equivalent to SSP-004184 7-68 mg/kg/day) either once daily or twice daily at the discretion of investigator for up to a maximum of 3 years or until the sponsor decided to stop the study.
Measure Participants	9
Mean (Standard Deviation) [mg/g dry tissue]	-1.0 (1.68)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SSP-004184AQ
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1232
	Comments	P-value was from paired t-test for post treatment timepoint versus baseline.
	Method	paired t-test
	Comments

3. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

FAS participants evaluable for this outcome.

Arm/Group Title	SSP-004184AQ
Arm/Group Description	Participants received SSP-004184AQ (magnesium salt of free acid or active form, that is, SSP-004184 [SPD602, FBS0701]) capsules orally at a total daily dose of 8-75 mg/kg/day (equivalent to SSP-004184 7-68 mg/kg/day) either once daily or twice daily at the discretion of investigator for up to a maximum of 3 years or until the sponsor decided to stop the study.
Measure Participants	7
Mean (Standard Deviation) [mg/g dry tissue]	-1.5 (2.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SSP-004184AQ
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1319
	Comments	P-value was from paired t-test for post treatment timepoint versus baseline.
	Method	paired t-test
	Comments

4. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SSP-004184AQ
Arm/Group Description	Participants received SSP-004184AQ (magnesium salt of free acid or active form, that is, SSP-004184 [SPD602, FBS0701]) capsules orally at a total daily dose of 8-75 mg/kg/day (equivalent to SSP-004184 7-68 mg/kg/day) either once daily or twice daily at the discretion of investigator for up to a maximum of 3 years or until the sponsor decided to stop the study.
Measure Participants	23
Baseline (n=23)	35.14 (12.242)
Change at Week 24 (Cycle 1) (n=14)	-0.41 (8.069)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SSP-004184AQ
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8061
	Comments	P-value was from paired t-test for log-transformed data at post treatment timepoint versus baseline.
	Method	paired t-test
	Comments

5. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

FAS participants evaluable for this outcome.

Arm/Group Title	SSP-004184AQ
Arm/Group Description	Participants received SSP-004184AQ (magnesium salt of free acid or active form, that is, SSP-004184 [SPD602, FBS0701]) capsules orally at a total daily dose of 8-75 mg/kg/day (equivalent to SSP-004184 7-68 mg/kg/day) either once daily or twice daily at the discretion of investigator for up to a maximum of 3 years or until the sponsor decided to stop the study.
Measure Participants	9
Mean (Standard Deviation) [milliseconds]	-3.47 (9.619)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SSP-004184AQ
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2297
	Comments	P-value was from paired t-test for log-transformed data at post treatment timepoint versus baseline.
	Method	paired t-test
	Comments

6. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

FAS participants evaluable for this outcome.

Arm/Group Title	SSP-004184AQ
Arm/Group Description	Participants received SSP-004184AQ (magnesium salt of free acid or active form, that is, SSP-004184 [SPD602, FBS0701]) capsules orally at a total daily dose of 8-75 mg/kg/day (equivalent to SSP-004184 7-68 mg/kg/day) either once daily or twice daily at the discretion of investigator for up to a maximum of 3 years or until the sponsor decided to stop the study.
Measure Participants	7
Mean (Standard Deviation) [milliseconds]	-3.91 (5.551)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SSP-004184AQ
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1248
	Comments	P-value was from paired t-test for log-transformed data at post treatment timepoint versus baseline.
	Method	paired t-test
	Comments

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SSP-004184AQ
Arm/Group Description	Participants received SSP-004184AQ (magnesium salt of free acid or active form, that is, SSP-004184 [SPD602, FBS0701]) capsules orally at a total daily dose of 8-75 mg/kg/day (equivalent to SSP-004184 7-68 mg/kg/day) either once daily or twice daily at the discretion of investigator for up to a maximum of 3 years or until the sponsor decided to stop the study.
Measure Participants	23
Baseline (n=23)	5353.38 (4588.423)
Change at Week 24 (Cycle 1) (n=12)	-395.82 (569.305)
Change at Week 48 (Cycle 1) (n=9)	-250.87 (452.327)
Change at Week 24 (Cycle 2) (n=7)	-384.03 (649.990)

Adverse Events

Time Frame	From start of study treatment up to the end of study (1 week after the end of treatment)
Adverse Event Reporting Description	An adverse event (AE) that occurred during the study was considered a treatment-emergent AE (TEAE) if it had a start date and time on or after the study treatment or if it had a start date before the date and time of the study treatment but increased in intensity on or after the date and time of the study treatment.
Arm/Group Title	SSP-004184AQ
Arm/Group Description	Participants received SSP-004184AQ (magnesium salt of free acid or active form, that is, SSP-004184 [SPD602, FBS0701]) capsules orally at a total daily dose of 8-75 mg/kg/day (equivalent to SSP-004184 7-68 mg/kg/day) either once daily or twice daily at the discretion of investigator for up to a maximum of 3 years or until the sponsor decided to stop the study.
All Cause Mortality
	SSP-004184AQ
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	SSP-004184AQ
	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis	1/30 (3.3%)	1
Infections and infestations
Bronchitis	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	SSP-004184AQ
	Affected / at Risk (%)	# Events
Total	25/30 (83.3%)
Gastrointestinal disorders
Nausea	4/30 (13.3%)	6
Abdominal pain upper	3/30 (10%)	3
Constipation	2/30 (6.7%)	2
Diarrhoea	2/30 (6.7%)	3
General disorders
Influenza like illness	5/30 (16.7%)	6
Asthenia	4/30 (13.3%)	8
Pyrexia	2/30 (6.7%)	5
Infections and infestations
Nasopharyngitis	5/30 (16.7%)	6
Pharyngitis	3/30 (10%)	3
Gastroenteritis	2/30 (6.7%)	4
Nervous system disorders
Paraesthesia	4/30 (13.3%)	5
Headache	3/30 (10%)	3
Psychiatric disorders
Depression	2/30 (6.7%)	2
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	4/30 (13.3%)	6
Cough	2/30 (6.7%)	2

Limitations/Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.