Clinical trial NCT05693909: A Trial Testing SP-420 in Subjects With Transfusion-dependent β-thalassemia
Official title: An Open-label, Dose-escalation, Dose-finding, and Proof-of-concept Trial of SP-420 in Subjects With Transfusion-dependent β-thalassemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Beta Thalassemia Major Anemia
Lead sponsor: Pharmacosmos A/S
Sponsor class: INDUSTRY
Collaborators: name: ICON plc
First posted: 2023-01-23
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn about SP-420 ability to remove iron from organs in subjects with transfusion-dependent β-thalassemia. The main questions it aims to answer are:

* How efficient is SP-420 in cleaning iron from the liver?
* How is the safety and tolerability of ascending doses of SP-420?

Participants will:

* Take medication three time weekly
* Attend up to 20 site visits
* Undergo MRI scans


Eligibility criteria: Inclusion Criteria:

1. Women and men aged ≥18 years
2. Transfusion-dependent β-thalassemia including HbE/β-thalassemia requiring iron chelation therapy (β-thalassemia with mutation and/or multiplication of α-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. β-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. LVEF on MRI \<56 % (echocardiography allowed if MRI not available)
14. A QTcF \>450 ms, 2nd or 3rd degree atrioventricular block, or incomplete left hemiblock, 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 (premenopausal and not surgically sterile) have to use highly efficient contraception (e.g. intrauterine devices, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release)) during the whole trial period and 4 weeks post-dosing. A sterile sole partner or sexual abstinence is also considered acceptable provided it reflects the usual and preferred lifestyle of the participant
25. Men, even if surgically sterilised, (i.e. status post vasectomy), who do not agree to practice effective barrier contraception during the entire trial period, or agrees to completely abstain from heterosexual intercourse
26. Any other laboratory abnormality, medical condition, or psychiatric disorder which, in the opinion of the Investigator, will put the subject's disease management at risk or may result in the subject being unable to comply with the trial requirements

Primary outcomes:
measure: To establish dose-response relationship of SP-420 for 24 weeks in the treatment of subjects with transfusion-dependent β-thalassemia
timeFrame: 24 weeks
Secondary outcomes:
measure: To assess the efficacy of SP-420 in clearing iron from the liver after 24 weeks treatment of subjects with transfusion-dependent β-thalassemia
timeFrame: 24 weeks
measure: To assess the efficacy of SP-420 in clearing iron from the liver after 12 and 48 weeks treatment of subjects with transfusion-dependent β-thalassemia
timeFrame: 12 and 48 weeks
measure: To assess the efficacy of SP-420 on serum (s-) ferritin
timeFrame: up to 48 weeks
measure: To assess the safety and tolerability of ascending doses of SP-420
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Pharmacosmos Investigational Site
Study officials:
affiliation: Pharmacosmos A/S
name: Pharmacosmos Clinical and non-clinical Department
role: STUDY_DIRECTOR
References: