Extending the treatment of Iron Overload

• Register: EUCTR
• Last refreshed on: 17 October 2016
• Main ID: EUCTR2011-006322-25-GB
• Date of registration: 14/08/2012
• Prospective Registration: Yes
• Primary sponsor: Shire Development LLC
• Public title: Extending the treatment of Iron Overload
• Scientific title: A Phase 2, Open-label, Multicentre, Extension Safety and Tolerability Study for Transfusionally Iron Overloaded Children, Adolescents and Adults Using SSP-004184 (SPD602).
• Date of first enrolment: 08/10/2012
• Target sample size: 1500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-006322-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Egypt, Italy, Lebanon, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Rachel Duncan
• Affiliation: Shire Pharmaceutical Development Ltd

• Name: Rachel Duncan
• Affiliation: Shire Pharmaceutical Development Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
For all subjects:

1. Subjects and/or parents willing and able to sign the approved informed consent/and assent (based on institutional guidelines).
2. An understanding, ability, and willingness to fully comply with study procedures and restrictions.
3. Has either completed a previous SSP-004184AQ study or prematurely discontinued (with agreement from the Investigator and Shire physician) from 1 of the SSP-004184AQ studies.
4. If applicable, female subjects should be either:
• Post-menopausal (12 consecutive months of spontaneous amenorrhea), or
• Surgically sterile, or
• 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:

5. Willing to discontinue all existing iron chelation therapies for a minimum period of 1 to 5 days prior to first dose of SSP-004184AQ.
6. (Note: This inclusion criterion is also applicable for subjects that were receiving chelators other than SSP-004184AQ in their feeder protocol.)
7. Serum ferritin >500 ng/mL at the Qualification and Enrollment Visit.
8. Liver iron concentration (LIC) =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.)
9. Mean of the previous 3 pre-transfusion hemoglobin concentrations =7.5 g/dL

Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1320
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion criteria:
For all subjects:

1. Unwilling to remain off all other existing chelation therapies during SSP-004184AQ dosing and for up to 24 hours from last dose.
2. A history of non-compliance in a prior FerroKin/Shire-sponsored SSP-004184AQ study (excluding dose suspensions that were medically warranted).
3. Cardiac MRI T2* <10.0 milliseconds at the Qualification and Enrollment Visit.
4. Cardiac left ventricular ejection fraction <50% at the Qualification and Enrollment Visit by MRI or below the locally determined normal range by echocardiography if MRI information is not available.
5. Evidence of clinically relevant oral, cardiovascular, gastrointestinal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow, dermatologic, hepatic, biliary (eg, chronic cholecystitis), or renal dysfunction where, in the opinion of the Investigator or the Shire Study Physician, treatment with SSP-004184AQ is relatively contraindicated.
6. Platelet count below 100,000/µL or absolute neutrophil count less than 1500/mm3 at the Qualification and Enrollment Visit.
7. Known sensitivity to any ingredient in the SSP-004184AQ formulation.
8. 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:

9. In younger subjects for whom MRI is not feasible, evidence of severe cardiac dysfunction, as assessed by the Investigator.
10. Non-elective hospitalization within the 30 days prior to receiving the first dose of SSP 004184AQ.
11. For subjects =18 years old: ALT >200 IU/L at the Qualification and Enrollment Visit.
OR
For subjects <18 years old: ALT >180 IU/L at the Qualification and Enrollment Visit.
12. For subjects =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 <40 mL/min.
OR
For subjects <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.
13. Use of any investigational agent within the 30 days prior to receiving the first dose of SSP-004184AQ.
14. Cardiac left ventricular ejection fraction below the locally determined normal range in the 12 months prior to Screening by
echocardiography or MRI or <50% at Baseline testing by MRI (Echocardiograph is acceptable for LVEF if MRI information is not available.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with transfusional iron overload due to hereditary anemias such as sickle cell disease, beta-thalassemia and Diamond-Blackfan anemia; aquired anemias such as Myelodysplastic Syndrome and other forms of bone marrow failure.
MedDRA version: 16.1 Level: LLT Classification code 10065974 Term: Chronic iron overload System Organ Class: 100000004861

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: SSP-004184AQ 50 mg Capsule
Product Code: SSP-004184AQ 50 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: deferitazole
CAS Number: 1173095-59-5
Current Sponsor code: SSP-004184AQ
Other descriptive name: (S)-4,5-dihydro-2[hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylate magnesium hydroxide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: SSP-004184AQ 100 mg Capsule
Product Code: SSP-004184AQ 100 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: deferitazole
CAS Number: 1173095-59-5
Current Sponsor code: SSP-004184AQ
Other descriptive name: (S)-4,5-dihydro-2[hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylate magnesium hydroxide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: SSP-004184AQ 200 mg Capsule
Product Code: SSP-004184AQ 200 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: deferitazole
CAS Number: 1173095-59-5
Current Sponsor code: SSP-004184AQ
Other descriptive name: (S)-4,5-dihydro-2[hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylate magnesium hydroxide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Product Name: SSP-004184AQ 250 mg Capsule
Product Code: SSP-004184AQ 250 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: deferitazole
CAS Number: 1173095-59-5
Current Sponsor code: SSP-004184AQ
Other descriptive name: (S)-4,5-dihydro-2[hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylate magnesium hydroxide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Product Name: SSP-004184AQ 375 mg Capsule
Product Code: SSP-004184AQ 375 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: deferitazole
CAS Number: 1173095-59-5
Current Sponsor code: SSP-004184AQ
Other descriptive name: (S)-4,5-dihydro-2[hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-m

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 3 years

Main Objective: Measure the extent and durability of SSP-004184AQ (SPD602)treatment effects; continue to assess the safety, tolerability and efficacy of SSP-004184AQ in subjects who received SSP-004184AQ in prior study; allow access and assess response to SSP-004184AQ in subjects randomised to another chelating therapy in a prior SSP-004184AQ study.

Pharmacokinetic parameters and their relationship to selected efficacy and safety parameters will also be explored. Further details regarding the pharmacokinetic analysis will be provided in the pharmacokinetic analysis plan.

Primary end point(s): Primary as per objectives

Secondary Objective: Not applicable

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: No

Secondary end point(s): No

Secondary ID(s)

SPD602-301

Source(s) of Monetary Support

Shire Development LLC