Clinical trial NCT03801889: SP-420 in Subjects With Transfusion-dependent Beta-Thalassemia or Other Rare Anemias
Official title: Multicenter, Open-label, 52 Week, Dose-escalation Study of SP 420 in Subjects With Transfusion-dependent Beta-Thalassemia or Other Rare Anemias
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Iron Overload
Beta-Thalassemia
Keywords: chelator
Lead sponsor: Abfero Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2019-01-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: The incidence of treatment-emergent Adverse Events (AEs)
timeFrame: Week 24
measure: The incidence of treatment-emergent Adverse Events (AEs)
timeFrame: Week 52
Secondary outcomes:
measure: Change in liver iron concentration (LIC) on R2-MRI from baseline
timeFrame: Week 24
measure: Change in liver iron concentration (LIC) on R2-MRI from baseline
timeFrame: Week 52
measure: Change in cardiac iron content (CIC) on T2*-MRI from baseline
timeFrame: Week 24
measure: Change in cardiac iron content (CIC) on T2*-MRI from baseline
timeFrame: Week 52
measure: Total iron removed by chelator (in mg) from baseline
timeFrame: Week 24
measure: Total iron removed by chelator (in mg) from baseline
timeFrame: Week 52
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University of Toronto- University Health Network
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: İzmir
country: Turkey
facility: Ege University Hospital
Study officials:
affiliation: American University of Beirut Medical Center
name: Ali Taher, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: