Transfusion-dependent ß-thalassemia MedDRA version: 20.1 Level: LLT Classification code 10054660 Term: Thalassemia beta System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: SP-420
Product Code: SP-420
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not yet assigned
CAS Number: 911714-45-9
Current Sponsor code: SP-420
Other descriptive name: (S)-4,5-
Sponsors
Pharmacosmos A/S
Eligibility
Sex/Gender
All
Inclusion criteria
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 90 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. ß-thalassemia with the structural Hb variants HbS and HbC 2. Cardiac MRI-T2 score 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 0.5 mg/mg at screening 12. Heart failure grade II, III and IV by NYHA 13. Left ventricular ejection fraction (LVEF) on MRI 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 ofchildbearing 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., permanent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary efficacy objective To establish dose-response relationship of SP-420 for 24 weeks in the treatment of subjects with transfusion-dependent ß-thalassemia ;Secondary Objective: Key-secondary efficacy objective To assess the efficacy of SP-420 in clearing iron from the liver after 24 weeks treatment of subjects with transfusion-dependent ß-thalassemia Secondary efficacy objective To assess the efficacy of SP-420 in clearing iron from the liver after 12 and 48 weeks treatment of subjects with transfusion-dependent ß-thalassemia To assess the efficacy of SP-420 in total body iron removal after 12 and 48 weeks treatment of subjects with transfusion-dependent ß-thalassemia To assess the efficacy of SP-420 on serum (s-) ferritin Secondary safety objective To assess the safety and tolerability of ascending doses of SP-420 ;Primary end point(s): Primary efficacy endpoint • Total body iron removed by SP-420 from baseline to week 24 ;Timepoint(s) of evaluation of this end point: Please refer to protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key-secondary efficacy endpoints • Change in liver iron concentration (LIC) measured by R2-magnetic resonance imaging (MRI) from baseline to week 24 Secondary efficacy endpoints • Change in LIC measured by R2-MRI from baseline to week 12 and week 48 • Total body iron removed by SP-420 from baseline to week 12 and week 48, and from week 24 to week 48 • Change in s-ferritin from baseline to weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 Secondary safety endpoints • Type and incidence of adverse events (AEs) ;Timepoint(s) of evaluation of this end point: Please refer to protocol | — |
Countries
Australia, Canada, Denmark, Greece, Italy, Lebanon, Oman, Qatar, Thailand, Türkiye, United Arab Emirates, United Kingdom
Contacts
Public ContactMartin Damm Olling
Pharmacosmos A/S
Outcome results
None listed