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

• Conditions: Transfusion-dependent ß-thalassemia; MedDRA version: 20.1Level: LLTClassification code 10054660Term: Thalassemia betaSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2022-002395-36-GR
• Lead Sponsor: Pharmacosmos A/S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-12-20
• Last Update Posted: 28 August 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 90

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 85
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1. ß-thalassemia with the structural Hb variants HbS and HbC
2. Cardiac MRI-T2 score <10 msec obtained within 2 weeks prior to baseline
3. S-ferritin <500 or >4000 ng/mL
4. Current malignancy with the exceptions of localised basal cell or squamous cell skin cancer or localised prostate cancer or is receiving immunotherapy, chemotherapy, or radiation therapy for a malignancy
5. Current myelodysplastic syndrome
6. Current biliary disorder
7. ALAT >4 times the upper limit of normal, decompensated cirrhosis, or ascites at screening
8. Past or ongoing history of clinically significant kidney disease
9. Creatinine greater than the upper limit of normal at screening
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
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., perman

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified