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

NCT03801889 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: SP-420-705
• Study Type: interventional
• Target: N/A
• Locations: 4 countries
• Sites: 4

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.

Conditions

Iron Overload; Beta-Thalassemia

Keywords

chelator

Outcome Measures

Primary Outcomes (2)

• The incidence of treatment-emergent Adverse Events (AEs)

  Week 24

• The incidence of treatment-emergent Adverse Events (AEs)

  Week 52

Secondary Outcomes (6)

• 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

Study Arms (3)

Cohort 1

EXPERIMENTAL

SP-420 initially at 28 mg/kg

Drug: SP-420

Cohort 2

EXPERIMENTAL

SP -20 initially at 56 mg/kg

Drug: SP-420

Cohort 3

EXPERIMENTAL

SP-420 initially at 84 mg/kg

Drug: SP-420

Interventions

SP-420 DRUG

Self-administered by mouth

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Abfero Pharmaceuticals, Inc: lead

Study Sites (4)

University of Toronto- University Health Network

Toronto, Canada

Location

American University of Beirut Medical Center

Beirut, Lebanon

Location

Siriraj Hospital

Bangkok, Thailand

Location

Ege University Hospital

Izmir, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Iron Overload; beta-Thalassemia

Interventions

SP-420

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Ali Taher, MD, PhD

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 14, 2019
• Study Start: August 1, 2020
• Primary Completion: September 1, 2022
• Study Completion: January 1, 2023
• Last Updated: October 5, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1); TH (1); TU (1); CA (1)