Clinical trial NCT01604941: Pharmacokinetics of SSP-004184 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Iron Overload Due to Repeated Red Blood Cell Transfusions
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-05-24
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

  1. Post-menopausal (12 consecutive months of spontaneous amenorrhea), or
  2. Surgically sterile, or
  3. 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:

  1. T2\* MRI \<10 ms
  2. 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

  1. Below the locally determined normal range in the 12 months prior to Screening by echocardiograph or MRI or
  2. \<50% at Baseline testing by MRI (echocardiograph is acceptable for LVEF if MRI information is not available).

Primary outcomes:
measure: Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, 12 and 24 weeks
measure: Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI
timeFrame: Baseline, 12 and 24 weeks
Secondary outcomes:
measure: Change From Baseline in LIC as Assessed by R2* MRI
timeFrame: Baseline, 12 and 24 weeks
measure: Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI
timeFrame: Baseline, 12 and 24 weeks
measure: Change From Baseline in Cardiac T2* Relaxation Rate, an MRI Parameter Used to Estimate Cardiac Iron Load
timeFrame: Baseline, 12 and 24 weeks
measure: Change From Baseline in Serum Ferritin
timeFrame: Baseline, 8 and 16 weeks
measure: Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC
timeFrame: 12 and 24 weeks
measure: Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC Adjusted For Transfusional Iron Intake
timeFrame: 12 and 24 weeks
measure: Number of Participants Classified as a Responder by R2* MRI Analysis of LIC
timeFrame: 12 and 24 weeks
measure: Number of Participants Classified as a Responder by R2* MRI Analysis of LIC Adjusted For Transfusional Iron Intake
timeFrame: 12 and 24 weeks
measure: Number of Participants Classified as a Responder by Serum Ferritin
timeFrame: 8 and 16 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Center for Cancer and Blood Diseases
state: California
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Cairo
country: Egypt
facility: Ain Shams University Pediatric Hospitals
city: Cairo
country: Egypt
facility: Cairo University Pediatric Hospitals
city: Genova
country: Italy
facility: Centro della Microcitemia e delle Anemie Congenite
state: Genoa
city: Orbassano
country: Italy
facility: San Luigi Hospital Thalassemia Centre
state: Torino
city: Cagliari
country: Italy
facility: Ospedale Regionale Microcitemie
city: Milan
country: Italy
facility: Ospedale Maggiore Policlinico
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: