A 24 week trial to study the safety and tolerability of SSP-004184 in the treatment of patients with longterm iron overload who need iron chelation therapy, with the option of 72 weeks further dosing.
- Conditions
- Patients with transfusional iron overload due to hereditary anemias such as sickle cell disease, ß-thalassemia and Diamond-Blackfan anemiaacquired anemias such as Myelodysplastic Syndrome and other forms of bone marrow failure.MedDRA version: 14.1Level: LLTClassification code 10065974Term: Chronic iron overloadSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2010-019645-25-GB
- Lead Sponsor
- Shire Development LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 50
1.Willing and able to sign the approved informed consent.
2.Age: 18-60 years old at Screening
3.Transfusional iron overload due to: hereditary anemias such as sickle cell disease, ß-thalassemia and Diamond-Blackfan anemia; acquired anemias such as Myelodysplastic Syndrome and other forms of bone marrow failure. Patients must also:
a.Be transfusion-dependent (8 or more transfusions annually) and
b.Require chronic treatment with deferoxamine, deferasirox, and/or deferiprone.
4.Willing to discontinue all existing iron chelation therapies for a minimum period of one to five days prior to first dose of SSP-004184, the 24 week duration of the study and 1 week after last dose for a total of approximately 26 weeks.
5.Serum ferritin > 500 ng/mL at Screening.
6.Baseline (Day -14 to Day -7) liver iron concentration (LIC) between =3.5 and <30 mg iron per g (equivalent, dry weight, liver) determined by FerriScan® MRI.
7.Baseline (Day -14 to Day -7) cardiac MRI T2* =10 milliseconds.
8.Mean of the previous three pre-transfusion hemoglobin concentrations = 7.5 g/dL.
9.Agrees to use an approved method of contraception from Screening and until 28 days after the last administration of the study drug. Agreed methods of contraception may include: condom; use of birth control pills, patches, implants or injections, diaphragm with vaginal spermicide, intrauterine device (IUD) and/or surgical sterilization (vasectomy or tubal ligation at least six months prior to dosing). Patients practicing abstinence must agree to use an approved method of contraception should they become sexually active during the study. A monthly pregnancy test will be performed on all female patients of child-bearing potential during the Screening and study period.
Requalification Inclusion Criteria (entry into 24 & 48 week extended dosing):
1.Willing to remain off all existing iron chelation therapies during FBS0701 dosing and 1 week after last dose for a total of approximately 50 - 98 weeks.
2.Have a serum ferritin above the upper limit of normal (>350 ng/mL) in the last assessment before Week 24/48.
3.Week 24/48 liver iron concentration (LIC) =2.0 mg iron per g (equivalent dry weight, liver) determined by FerriScan® MRI.
4.Week 24/48 cardiac MRI T2* =10 milliseconds.
5.Agree to continue to use an approved method of contraception until 28 days after the last administration of SSP-004184.
6.In the opinion of the Principal Investigator, sufficient compliance with study drug dosing to support continued use of SSP-004184.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.As a result of medical review, physical examination or Screening investigations, the Principal Investigator considers the patient unfit for the study.
2.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.)
3.Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow or skin disorder as determined by the Investigator.
4.Evidence of significant renal insufficiency; e.g., 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.
5.Cardiac left ventricular ejection fraction:
a.Outside the locally determined normal range in the 12 months prior to Screening by echocardiography or MRI or
b.<50% at Baseline testing by MRI
6.Known sensitivity to magnesium stearate, croscarmellose sodium or FBS0701.
7.Platelet count below 100,000/µL or absolute neutrophil count less than 1500/mm3 at Screening
8.Liver Function Tests
a.ALT >5 times the local upper limit of normal on two occasions in the previous 12 months or
b.ALT > 200 IU at Screening
9.Use of any investigational agent within the 30 days prior to the Baseline testing.
Requalification Exclusion Criteria (entry into 24 & 48 week extended dosing):
1.Has restarted prior chelation therapy. (NOTE: Ideally, patients will move directly from the initial dosing phase to the extended dosing phase with no pause in study drug dosing. Should there be an administrative need to interrupt study treatment, the patient may be allowed to remain off all chelator therapy for a maximum of 3 weeks prior to starting the extended phase of the study, should the Medical Monitor and the patient’s Principal Investigator deem it safe and clinically reasonable to do so.)
2.Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow or skin disorder as determined by the Investigator which in the view of the Investigator and the Medical Monitor represents an unacceptable risk to the patient.
3.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 less than 60 mL/min in the last assessment prior to the Week 24/48 visit.
4.Platelet count below 100,000/µL or absolute neutrophil count less than 1500/mm3 in the last assessment prior to the Week 24/48 visit.
5.Serum ALT >200 IU/L in the last assessment prior to the Week 24/48 visit
6.At Week 48 only: Left Ventricular Ejection Fraction <55% by MRI
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method