An open-label, dose-escalation, dose-finding, and proof-of-concept trial of SP-420 in subjects with transfusion-dependent ß-thalassemia

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 84

Inclusion Criteria

1. Women and men aged =18 years, 2. Transfusion-dependent ß-thalassemia including HbE/ß-thalassemia requiring iron chelation therapy (ß-thalassemia with mutation and/or multiplication of a-globin is allowed), 3. On a stable dose of iron chelation for at least 4 weeks prior to screening, 4. Weight =35 kg at screening, 5. 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 trial, 6. Transfusion iron overload defined as LIC =5 and =20 mg/g dw on the R2-MRI obtained within 2 weeks prior to baseline, 7. Subject has been treated and followed for at least the past 6 months in a specialised centre that maintained detailed medical records, including transfusion and iron chelation histories, 8. Willingness to participate and signing the informed consent form

Exclusion Criteria

1. ß-thalassemia with the structural Hb variants HbS and HbC, 10. Estimated glomerular filtration rate eGFR <60 mL/min/1.73 m2, 11. Urine protein to creatinine ratio >0.5 mg/mg at screening, 12. Heart failure grade II, III and IV by NYHA, 13. Left ventricular ejection fraction (LVEF) on MRI <56 % (echocardiography allowed if MRI not available), 14. A QTcF >450 ms, 2nd or 3rd degree atrioventricular block, complete left bundle branch block, or the presence of clinically significant abnormalities as determined by the Investigator at screening, 15. Hypertransfused defined as more than 6 units/month in average for the last 6 months prior to screening, 16. Ongoing symptoms of neuropathy, including peripheral sensory neuropathy, peripheral motor neuropathy, or paresthesia at screening, 17. Platelet count <100×109/L at screening, 18. History of hypersensitivity to an iron chelator (investigational or marketed) or excipients, 19. Documented history of non-compliance to chelation therapy within past 2 years, 2. Cardiac MRI-T2 score <10 msec obtained within 2 weeks prior to baseline, 20. Received another investigational drug within 30 days or investigational antibody within 90 days before screening, 21. Treatment with prohibited medication: iron, aluminium containing antacid therapies, systemic corticosteroids (topical and pulmonary corticosteroids are allowed), oral bisphosphonates, chronic use of high dose NSAIDs (as needed and low dose acetylsalicylic acid are allowed), drugs with known renal toxicity, drugs with known QTc prolongation, potent UGT inducers (e.g. rifampicin, phenytoin, phenobarbital, ritonavir) within 7 days prior to baseline, 22. Initiation of treatment with luspatercept within 6 months prior to screening (luspatercept is allowed if initiated and dose is stable at least 6 months prior to screening), 23. Subject unable to undergo trial assessments including MRI, e.g. who are claustrophobic to MRI, have a cardiac pacemaker, ferromagnetic metal implants other than those approved as safe for use in MR scanners (e.g. some types of aneurysm clips, and shrapnel), and subjects who are obese (exceeding the equipment limits), 24. Pregnant or nursing women. In order to avoid pregnancy, women of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) have to use highly efficient contraception (e.g., combined [estrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, or transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, or implantable], intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, or vasectomised partner) during the whole trial period and 4 weeks post-dosing. A sterile sole partner (i.e., permanently sterile by bilateral orchidectomy) or abstinence from heterosexual intercourse is also considered acceptable provided it reflects the usual and preferred lifestyle of the participant. Postmenopausal woman, defined as a woman who has experienced 12 consecutive months without menstruation without any alternative medical cause, do not need to use contraception, 25. Men who do not agree to practice effective barrier contraception during the entire trial period, or agrees to completely abstain from heterosexual inte

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials

A study of open administration of a drug, which removes iron from the body of patients with transfusion-dependent ß-thalassemia, aiming to find the most appropriate dose through use of different dose levels in different patients

Phase 1

Pharmacosmos A/S

Updated 8/28/2023