SP-420 in Subjects With Transfusion-dependent Beta-Thalassemia or Other Rare Anemias

Study Overview
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Brief Summary
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The purpose of this study is to test the safety and tolerability of SP-420 and it's efficacy in terms of lowering iron in subjects with Beta-thalassemia or other rare anemias who need regular blood transfusions.

Official Title
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Multicenter, Open-label, 52 Week, Dose-escalation Study of SP 420 in Subjects With Transfusion-dependent Beta-Thalassemia or Other Rare Anemias

Conditions
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Iron Overload, Beta-Thalassemia

Intervention / Treatment
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* Drug: SP-420


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years old Iron-overload secondary to β-thalassemia (homozygote or compound heterozygote) or other rare anemias (e.g., aplastic anemia, pure red-cell dysplasia ) requiring chronic RBC transfusions and iron chelation therapy On a stable dose of iron chelation for at least 4 weeks prior to screening visit Weight ≥35 kg at screening Willing to discontinue current iron chelation therapy 7 days (± 3 days) prior to the first dose of SP-420 and for the duration of the current study LIC ≥5 and ≤25 mg/g dry weight on the R2-MRI obtained within 2 weeks prior to the baseline visit Cardiac T2* score > 12 msec obtained on the MRI obtained within 2 weeks prior to the baseline visit Exclusion Criteria: Pregnant or breast-feeding Current malignancy with the exceptions of localized basal cell or squamous cell skin cancer or localized prostate cancer or is receiving immunotherapy, chemotherapy or radiation therapy for a malignancy Current myelodysplastic syndrome Alanine aminotransferase (ALT) >4 times the upper limit of normal, decompensated cirrhosis, or ascites at screening Past history of clinically significant kidney disease (per the Principal Investigator) Serum creatinine greater than the upper limit of normal during screening Urine protein to creatinine ratio > 0.5 mg/mg during screening Ongoing symptoms of cardiac dysfunction or failure Ongoing symptoms of neuropathy, including peripheral sensory neuropathy, peripheral motor neuropathy, or paresthesia at screening Received another investigational drug within 30 days or investigational antibody within 90 days of Day 1 of the study Other condition that, in the opinion of the PI, would interfere with the conduct of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is a multi-center, open-label, dose-escalation study designed to evaluate the safety, tolerability, and iron clearing efficacy of SP 420 administered three-times per week in subjects with transfusion-dependent beta-thalassemia or other rare anemias. Approximately 24 subjects are to be enrolled in 3 cohorts (doses of 28 mg/kg, 56 mg/kg and 84 mg/kg) of approximately 8 subjects each. Based upon the results from lower dose cohorts, if needed the size of latter cohorts may be increased to improve the power of the study to detect efficacy to approximately 74 subjects in total.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>SP-420 initially at 28 mg/kg | Drug: SP-420<br>* Self-administered by mouth<br>|
| Experimental: Cohort 2<br>SP -20 initially at 56 mg/kg | Drug: SP-420<br>* Self-administered by mouth<br>|
| Experimental: Cohort 3<br>SP-420 initially at 84 mg/kg | Drug: SP-420<br>* Self-administered by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of treatment-emergent Adverse Events (AEs) |  | Week 24 | 
| The incidence of treatment-emergent Adverse Events (AEs) |  | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in liver iron concentration (LIC) on R2-MRI from baseline |  | Week 24 | 
| Change in liver iron concentration (LIC) on R2-MRI from baseline |  | Week 52 | 
| Change in cardiac iron content (CIC) on T2*-MRI from baseline |  | Week 24 | 
| Change in cardiac iron content (CIC) on T2*-MRI from baseline |  | Week 52 | 
| Total iron removed by chelator (in mg) from baseline |  | Week 24 | 
| Total iron removed by chelator (in mg) from baseline |  | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chelator