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

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Transfusional Iron Overload Beta-thalassemia
Intervention:	Drug: SPD602 (FBS0701, SSP-004184)

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

Description

SPD602 16 mg/kg/Day

Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.

SPD602 32 mg/kg/Day

Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.

Participant Flow: Overall Study

	SPD602 16 mg/kg/Day	SPD602 32 mg/kg/Day
STARTED	24	27
COMPLETED	17	18
NOT COMPLETED	7	9
Withdrawal by Subject	5	3
Adverse Event	1	2
Physician Decision	0	3
Not specified	1	1

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subjects who received any amount of investigational product.

Reporting Groups

	Description
SPD602 16 mg/kg/Day	Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.
SPD602 32 mg/kg/Day	Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.
Total	Total of all reporting groups

Baseline Measures

	SPD602 16 mg/kg/Day	SPD602 32 mg/kg/Day	Total
Overall Participants Analyzed [Units: Participants]	24	27	51

Age [Units: Participants]
<=18 years	0	1	1
Between 18 and 65 years	24	26	50
>=65 years	0	0	0

Age [Units: Years] Mean (Standard Deviation)	28.7 (8.60)	28.4 (7.11)	28.5 (7.77)

Gender [Units: Participants]
Female	12	14	26
Male	12	13	25

Outcome Measures

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1. Primary:

Change From Baseline in Liver Iron Concentration (LIC) at 96 Weeks [ Time Frame: Baseline and 96 weeks ]

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2. Secondary:

Maximum Plasma Concentration (Cmax) of SPD602 [ Time Frame: 92 weeks ]

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3. Secondary:

Area Under The Steady-state Plasma Concentration-time Curve (AUC) of SPD602 [ Time Frame: 92 weeks ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.

More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Results Point of Contact:

Name/Title: Study Physician
Organization: Shire Development LLC
phone: 1 866 842 5335

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

Responsible Party:	Shire
ClinicalTrials.gov Identifier:	NCT01186419 History of Changes
Other Study ID Numbers:	SPD602-201 2010-019645-25 ( EudraCT Number ) FBS0701-CTP-04 ( Other Identifier: Ferrokin )
Study First Received:	August 19, 2010
Results First Received:	April 23, 2015
Last Updated:	June 3, 2015