- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01604941
Pharmacokinetics of SSP-004184 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy
A Phase 2, 24 Week, Open Label, Multi-Center Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SSP-004184 (SPD602) in the Treatment of Chronic Iron Overload Requiring Chelation Therapy
The purpose of this study is to evaluate SSP-004184AQ in patients with transfusional iron overload whose primary diagnosis is hereditary or congenital anemia.
SSP-004184AQ is an iron chelator under development for chronic daily oral administration to patients with transfusional iron overload.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M5G 2C4
- Toronto General Hospital
-
-
-
-
-
Cairo, Egypt
- Ain Shams University Pediatric Hospitals
-
Cairo, Egypt
- Cairo University Pediatric Hospitals
-
-
-
-
-
Cagliari, Italy, 09121
- Ospedale Regionale Microcitemie
-
Milan, Italy, 20122
- Ospedale Maggiore Policlinico
-
-
Genoa
-
Genova, Genoa, Italy, 16128
- Centro della Microcitemia e delle Anemie Congenite
-
-
Torino
-
Orbassano, Torino, Italy, 10043
- San Luigi Hospital Thalassemia Centre
-
-
-
-
-
Beirut, Lebanon
- American University of Beirut Medical Center
-
-
-
-
California
-
Los Angeles, California, United States, 90027
- Children'S Center For Cancer And Blood Diseases
-
-
Illinois
-
Chicago, Illinois, United States, 60611
- Ann & Robert H. Lurie Children's Hospital of Chicago
-
-
New York
-
New York, New York, United States, 10065
- Weill Cornell Medical College
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Willing and able to sign the approved informed consent.
- Age: 18-60 years old, inclusive, at Screening.
- Subjects who have received more than 20 transfusions in their lifetime and who have transfusional iron overload requiring chronic treatment with an iron chelator. N.B.: Sickle Cell Disease subjects receiving regular exchange transfusions and iron overloaded subjects with thalassemia intermedia who are receiving regular transfusions (transfusion dependent thalassemia intermedia) are eligible.
- Willing to discontinue all existing iron chelation therapies for a minimum period of one to five days prior to first dose of SSP-004184AQ, the 24 week duration of the study and 1 week after last dose for a total of approximately 26 weeks.
- Willing to fast two hours prior to and one hour after each dose.
- Serum ferritin >500ng/mL at Screening.
- Baseline liver iron concentration is greater than or equal to 5mg iron per g (equivalent dry weight, liver)determined by FerriScan® R2 MRI.
- Mean of the previous three pre-transfusion hemoglobin concentrations is greater than or equal to 7.5g/dL.
Adult female subjects should be:
- Post-menopausal (12 consecutive months of spontaneous amenorrhea), or
- Surgically sterile, or
- Females of child-bearing potential must have a negative beta-HCG pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit.
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.
Exclusion Criteria:
- As a result of medical review, physical examination, or Screening investigations, the Principal Investigator (PI) considers the subject unfit for the study.
- Non-elective hospitalization within the 30 days prior to Baseline testing.
- Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, biliary, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow, or skin disorder that contraindicates dosing with SSP-004184AQ.
- Iron overload from causes other than transfusional siderosis.
- 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 <60mL/min.
Severe iron overload including:
- T2* MRI <10 ms
- liver iron concentration by FerriScan R2 MRI >30mg/g liver (dw)
- Known sensitivity to magnesium stearate, croscarmellose sodium or SSP-004184AQ.
- Platelet count below 100,000/μL or absolute neutrophil count less than 1500/mm3 at Screening.
- Insufficient venous access that precludes prescribed blood draws for safety laboratory assessments.
- ALT at Screening >200 IU/L.
- Use of any investigational agent within the 30 days prior to the Baseline testing.
- Pregnant or lactating females.
Cardiac left ventricular ejection fraction
- Below the locally determined normal range in the 12 months prior to Screening by echocardiograph or MRI or
- <50% at Baseline testing by MRI (echocardiograph is acceptable for LVEF if MRI information is not available).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: SPD602
50 mg/kg/day orally twice daily for 24 weeks
|
50 mg/kg/day orally twice daily for 24 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)
Time Frame: Baseline, 12 and 24 weeks
|
The efficacy of SPD602 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.
Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
|
Baseline, 12 and 24 weeks
|
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI
Time Frame: Baseline, 12 and 24 weeks
|
The efficacy of SPD602 was assessed by determining LIC and adjusting for transfusional iron intake.
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.
For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake.
Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
|
Baseline, 12 and 24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in LIC as Assessed by R2* MRI
Time Frame: Baseline, 12 and 24 weeks
|
The efficacy of SPD602 was assessed by determining LIC.
Abdominal MRI data were collected by using R2* standard procedures (liver and pancreas) and used to determine LIC.
A negative change from baseline indicates that LIC decreased.
Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
|
Baseline, 12 and 24 weeks
|
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI
Time Frame: Baseline, 12 and 24 weeks
|
The efficacy of SPD602 was assessed by determining LIC and adjusting for transfusional iron intake.
Abdominal MRI data were collected by using R2* standard procedures (liver and pancreas) and used to determine LIC.
A negative change from baseline indicates that LIC decreased.
For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake.
Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
|
Baseline, 12 and 24 weeks
|
Change From Baseline in Cardiac T2* Relaxation Rate, an MRI Parameter Used to Estimate Cardiac Iron Load
Time Frame: Baseline, 12 and 24 weeks
|
The efficacy of SPD602 was assessed by estimating cardiac iron load.
T2* data from cardiac MRI were collected by using standard procedures and used as an estimate of cardiac iron load.
T2* is an MR relaxation parameter that is reported in milliseconds.
Iron within a tissue decreases homogeneity of the magnetic field and shortens the T2* relaxation rate (Anderson, 2001).
Low cardiac T2* values are associated with increased risk of heart failure (Kirk, 2009).
A negative change from baseline in the T2* relaxation rate indicates that iron load increased.
Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
|
Baseline, 12 and 24 weeks
|
Change From Baseline in Serum Ferritin
Time Frame: Baseline, 8 and 16 weeks
|
Serum ferritin levels were determined from serum biochemistry analyses.
A negative change from baseline indicates that serum ferritin decreased.
|
Baseline, 8 and 16 weeks
|
Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC
Time Frame: 12 and 24 weeks
|
A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value.
LIC was assessed by abdominal MRI with the FerriScan R2 according to standard procedures.
Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
|
12 and 24 weeks
|
Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC Adjusted For Transfusional Iron Intake
Time Frame: 12 and 24 weeks
|
A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value.
LIC was assessed by abdominal MRI with the FerriScan R2 according to standard procedures, and the results were adjusted for transfusional iron intake.
Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake.
|
12 and 24 weeks
|
Number of Participants Classified as a Responder by R2* MRI Analysis of LIC
Time Frame: 12 and 24 weeks
|
A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value.
LIC was assessed by abdominal MRI with the R2* according to standard procedures (liver and pancreas).
Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
|
12 and 24 weeks
|
Number of Participants Classified as a Responder by R2* MRI Analysis of LIC Adjusted For Transfusional Iron Intake
Time Frame: 12 and 24 weeks
|
A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value.
LIC was assessed by abdominal MRI with the R2* according to standard procedures (liver and pancreas), and the results were adjusted for transfusional iron intake.
Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake.
|
12 and 24 weeks
|
Number of Participants Classified as a Responder by Serum Ferritin
Time Frame: 8 and 16 weeks
|
A responder was defined as a participant whose observed serum ferritin level at the measured time point was less than the baseline value.
Serum ferritin levels were determined from serum biochemistry analyses.
|
8 and 16 weeks
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SPD602-203
- FBS0701-CTP-16 (OTHER: Ferrokin)
- 2011-005675-16 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Iron Overload Due to Repeated Red Blood Cell Transfusions
-
ApoPharmaCompletedIron Overload Due to Repeated Red Blood Cell TransfusionsUnited States, Canada, Greece, Italy
-
ShireTerminatedIron Overload Due to Repeated Red Blood Cell TransfusionsCanada, United States, Thailand, Italy, United Kingdom
-
Sheba Medical CenterHadassah Medical Organization; Kaplan Medical Center; Tel Aviv Medical Center; Ziv...CompletedMyelodysplastic Syndrome With Low-grade Lesions | Iron Overload Due to Repeated Red Blood Cell TransfusionsIsrael
-
Novartis PharmaceuticalsCompletedChronic Iron Overload Due to Transfusion-dependant AnemiasItaly, Austria, Thailand, Spain, Germany, Mexico, Malaysia, Greece, United Kingdom, France, Saudi Arabia, United Arab Emirates, Lebanon, Russian Federation, United States, Argentina
-
Mayo ClinicArizona State UniversityCompletedAnemia | Oncology | Ambulatory Care | Hematology | Red Blood Cell TransfusionsUnited States
-
Poznan University of Physical EducationRecruitingIron Metabolism Disorders | Oxidative Stress | Red Blood Cell DisorderPoland
-
Iowa State UniversityCompletedIron-deficiency | Iron Deficiency Anemia | Iron Deficiency Anemia Treatment | Iron Deficiency Anaemia Due to Dietary CausesUnited States
-
Sunnybrook Health Sciences CentrePrincess Margaret Hospital, Canada; Juravinski Cancer CenterUnknownQuality of Life | Myelodysplastic Syndromes (MDS) | Red Blood Cell (RBC) TransfusionsCanada
-
Texas Tech University Health Sciences Center, El...CompletedIron-deficiency | Iron Deficiency Anemia | Iron Deficiency Anemia Treatment | Iron Deficiency Anemia Due to Blood LossUnited States
-
NovartisCompletedMyelodysplastic Syndromes | Hemoglobinopathies | Diamond-Blackfan Anemia | Transfusional Iron Overload | Other Inherited or Acquired Anaemia | MPD Syndrome | Other Rare AnaemiasAustralia
Clinical Trials on SPD602
-
ShireCompleted
-
ShireCompleted
-
ShireCompletedImpaired Renal FunctionUnited States
-
ShireCompleted
-
ShireTerminatedIron Overload Due to Repeated Red Blood Cell TransfusionsCanada, United States, Thailand, Italy, United Kingdom
-
ShireCompletedBeta-thalassemia | Transfusional Iron OverloadUnited States, United Kingdom, Italy, Thailand, Turkey
-
ShireCompletedHealthy | Hepatic ImpairmentUnited States
-
ShireTerminatedBeta-Thalassemia | Transfusional Iron OverloadUnited States, Lebanon, Canada, Italy, Turkey
-
ShireWithdrawn
-
ShireWithdrawnMetabolic Diseases | Iron Metabolism Disorders | Iron Overload | Beta-thalassemia | Transfusional Hemosiderosis | Transfusional Iron Overload | Iron Chelation