Pilot Study to Assess the Safety, PK and Iron Chelating Activity of DST-0509 (Deferasirox) in Thalassemia Patients Refractory to Chelation

NCT03637556 | Completed Phase 2 FDA Drug

• 1 other identifier: DST-0509-201
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 4

Brief Summary

This study is a multicenter, open-label, two-period crossover design that evaluates the safety, tolerability, pharmacokinetics and preliminary evidence of iron chelating activity of DST-0509 as compared to Jadenu and Exjade in transfusion-dependent thalassemia patients with transfusional iron overload, requiring iron chelation therapy and demonstrating an inadequate response to Jadenu or Exjade for greater than 3 months duration. Up to 36 patients will be evaluated (18 in each treatment arm), however, the balanced randomization may enroll fewer patients based on recruitment status.

Conditions

Thalassemia Major

Keywords

thalassemia; iron; chelation; deferasirox; DST-0509; transfusion

Outcome Measures

Primary Outcomes (2)

• diarrhea %

  safety tolerability

  Up to Day 70

• Ferritin (mcg/L)

  iron chelating activity

  Up to Day 63

Secondary Outcomes (3)

• Area Under the Curve (AUC), mg*h/L

  Days 1, 7, 28, 36, 42 and 63

• Maximum concentration (Cmax), mg/L

  Days 1, 7, 28, 36, 42 and 63

• Time to maximum concentration (Tmax), h

  Days 1, 7, 28, 36, 42 and 63

Study Arms (3)

DST-0509

EXPERIMENTAL

DST-0509 (deferasirox) will be supplied in 360 mg, 180 mg and 90 mg tablets. DST-0509 is taken once daily with food; the first dose will be taken at Visit 3 (Day 1) and the final dose will be taken at Visit 10 (Day 63).

Drug: DST-0509

Jadenu

ACTIVE COMPARATOR

Jadenu is commercially available as tablets and will be provided by the patient with their ongoing prescription. Dosing will be at equivalent (mg for mg) doses of DST-0509 or Jadenu. Jadenu is taken once daily with or without a light meal. However, Jadenu can be administered according to the patient's current prescription regimen. The first dose will be taken at Visit 3 (Day 1) and the final dose will be taken at Visit 10 (Day 63).

Drug: Jadenu

Exjade

ACTIVE COMPARATOR

Exjade is commercially available as tablets and Exjade as tablets for oral suspension and will be provided by the patient with their ongoing prescription. Dosing will be at equivalent (mg for mg) doses of DST-0509 or Jadenu. If converting from Exjade, the dose will be scaled for each treatment by 28 mg/40 mg (treatment/Exjade). Jadenu and Exjade are taken once daily, Jadenu is taken with or without a light meal, and Exjade is recommended to be taken without food. However, either Jadenu or Exjade can be administered according to the patient's current prescription regimen. The first dose will be taken at Visit 3 (Day 1) and the final dose will be taken at Visit 10 (Day 63).

Drug: Exjade

Interventions

DST-0509 DRUG

Novel iron chelator with improved absorption characteristics

Also known as: deferasirox tablets

DST-0509

Jadenu DRUG

Commercial iron chelator with standard absorption characteristics

Also known as: deferasirox tablets

Jadenu

Exjade DRUG

Commercial iron chelator with standard absorption characteristics

Also known as: deferasirox oral suspension

Exjade

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent or assent as appropriate obtained prior to any study-related procedure being performed;
• Patients at least 8 years of age or older at the time of consent or assent;
• Patient with TDT syndrome and iron overload currently receiving iron chelation therapy with Jadenu or Exjade and demonstrating inadequate response assessed with serum ferritin and LIC;
• At least 8 or more blood transfusions in the past year;
• Survival expected of \>12 months;
• Patient previously on dual iron chelation therapy will be transfered to iron chelation monotherapy ,stable dosing with Jadenu or Exjade for ≥1month prior to screening and receiving doses in the maximal dose range per day (e.g., Jadenu: \>21 mg/kg or Exjade: \>30 mg/kg, with specific doses in these ranges prescribed at the physician's discretion);
• Serum ferritin levels that are persistently \>800 mcg/L determined by 2 separate assessments during screening over the previous 2-4 weeks prior to study treatment and not showing a decreasing trend over these weeks OR, an LIC of \>5 mg Fe/g dw measured by MRI in the 52 weeks prior to study entry, OR clearly identified as a poor responder in medical records within 3 months prior to the study
• Compliant with chelation therapy in the 3 months prior to enrollment in the opinion of the Investigator; has taken at least 75% of medication prescribed on a regular basis was taken (Investigator enquiry into patient prescription refill records, preferably 3 months if available, SICT scores); and
• Willing to comply with chelation therapy for the duration of the study;
• The determination of compliance is at the discretion of the investigator.
• Agree not to use other anti-chelating agents concurrently;
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1;
• Women of childbearing potential (WOCBP) must use an adequate method of birth control (double barrier, e.g. hormonal control and barrier contraception) at least 28 days prior to the first administration of the study drug, during the study and for at least 30 days after the last dose of the study drug;
• Male patients whose partners are WOCBP must use an adequate method of birth control (double barrier control) at least 28 days prior to the first administration of the study drug, during the study and for at least 30 days after the last dose of the study drug; and
• Patient is willing and able to comply with all protocol required visits and assessments.

You may not qualify if:

• Females of childbearing potential not on an adequate method of birth control, or who are pregnant or lactating;
• History of non-compliance with chelation therapy (determined by the investigator).
• Known history of human immunodeficiency virus (HIV)
• Active hepatitis B virus (HBV), hepatitis C virus (HCV), or other known active viral hepatitis;
• Screening blood counts as follows:
• Absolute neutrophil count \< 1,000/μL
• Platelets \< 50,000/μL
• Hemoglobin \< 7 g/dL (transfusion support is permitted);
• Screening chemistry values as follows:
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) \> 3 × upper limit of the normal reference range (ULN)
• Total bilirubin \> 5 × ULN
• Creatinine \> 1.5 × ULN
• Urine protein/creatinine ratio (UPCR) \> 0.5 mg/mg
• Albumin \< 2.8 g/dL;
• History of congestive heart failure New York Heart Association (NYHA) class III or IV or uncontrolled hypertension at screening;

Sponsors & Collaborators

• DisperSol Technologies, LLC: lead

Study Sites (4)

Weill Cornell Medicine, New York-Presbyterian Hospital

New York, New York, 10065, United States

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

Thalassemia Center Faculty of Medicine Siriraj Hospital

Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200, Thailand

Location

MeSH Terms

Conditions

beta-Thalassemia; Thalassemia

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

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

Model Details: open-label, two-period cross-over

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: August 20, 2018
• Study Start: August 20, 2019
• Primary Completion: June 8, 2021
• Study Completion: August 16, 2021
• Last Updated: February 1, 2022

Record last verified: 2022-01

Locations

US (1); TH (3)