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A Trial Testing SP-420 in Subjects With Transfusion-dependent β-thalassemia

Primary Purpose

Beta Thalassemia Major Anemia

Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
SP-420
Sponsored by
Pharmacosmos A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Beta Thalassemia Major Anemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Women and men aged ≥18 years Transfusion-dependent β-thalassemia including HbE/β-thalassemia requiring iron chelation therapy (β-thalassemia with mutation and/or multiplication of α-globin is allowed) On a stable dose of iron chelation for at least 4 weeks prior to screening Weight ≥35 kg at screening 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 Transfusion iron overload defined as LIC ≥5 and ≤20 mg/g dw on the R2-MRI obtained within 2 weeks prior to baseline 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 Willingness to participate and signing the informed consent form Exclusion Criteria: β-thalassemia with the structural Hb variants HbS and HbC Cardiac MRI-T2* score <10 msec obtained within 2 weeks prior to baseline S-ferritin <500 or >4000 ng/mL* 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 Current myelodysplastic syndrome Current biliary disorder ALAT >4 times the upper limit of normal, decompensated cirrhosis, or ascites at screening Past or ongoing history of clinically significant kidney disease Creatinine greater than the upper limit of normal at screening Estimated glomerular filtration rate eGFR <60 mL/min/1.73 m2 Urine protein to creatinine ratio >0.5 mg/mg at screening Heart failure grade II, III and IV by NYHA LVEF on MRI <56 % (echocardiography allowed if MRI not available) 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 Hypertransfused defined as more than 6 units/month in average for the last 6 months prior to screening Ongoing symptoms of neuropathy, including peripheral sensory neuropathy, peripheral motor neuropathy, or paresthesia at screening Platelet count <100×109/L at screening History of hypersensitivity to an iron chelator (investigational or marketed) or excipients Documented history of non-compliance to chelation therapy within past 2 years Received another investigational drug within 30 days or investigational antibody within 90 days before screening 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 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) 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) 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 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 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

Sites / Locations

  • Pharmacosmos Investigational SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

SP-420, 28 mg/kg, three times weekly for 48 weeks

SP-420, 56 mg/kg, three times weekly for 48 weeks

SP-420, 84 mg/kg, three times weekly for 48 weeks

Outcomes

Primary Outcome Measures

To establish dose-response relationship of SP-420 for 24 weeks in the treatment of subjects with transfusion-dependent β-thalassemia
Total body iron removed by SP-420 from baseline to week 24

Secondary Outcome Measures

To assess the efficacy of SP-420 in clearing iron from the liver after 24 weeks treatment of subjects with transfusion-dependent β-thalassemia
Change in liver iron concentration (LIC) measured by R2-magnetic resonance imaging (MRI) from baseline to week 24
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
Change in LIC measured by R2-MRI from baseline to week 12 and week 48
To assess the efficacy of SP-420 on serum (s-) ferritin
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
To assess the safety and tolerability of ascending doses of SP-420
Type and incidence of adverse events (AEs)

Full Information

First Posted
December 22, 2022
Last Updated
October 18, 2023
Sponsor
Pharmacosmos A/S
Collaborators
ICON plc
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1. Study Identification

Unique Protocol Identification Number
NCT05693909
Brief Title
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

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 4, 2023 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacosmos A/S
Collaborators
ICON plc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Beta Thalassemia Major Anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
SP-420, 28 mg/kg, three times weekly for 48 weeks
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
SP-420, 56 mg/kg, three times weekly for 48 weeks
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
SP-420, 84 mg/kg, three times weekly for 48 weeks
Intervention Type
Drug
Intervention Name(s)
SP-420
Intervention Description
Capsules for oral intake
Primary Outcome Measure Information:
Title
To establish dose-response relationship of SP-420 for 24 weeks in the treatment of subjects with transfusion-dependent β-thalassemia
Description
Total body iron removed by SP-420 from baseline to week 24
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
To assess the efficacy of SP-420 in clearing iron from the liver after 24 weeks treatment of subjects with transfusion-dependent β-thalassemia
Description
Change in liver iron concentration (LIC) measured by R2-magnetic resonance imaging (MRI) from baseline to week 24
Time Frame
24 weeks
Title
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
Description
Change in LIC measured by R2-MRI from baseline to week 12 and week 48
Time Frame
12 and 48 weeks
Title
To assess the efficacy of SP-420 on serum (s-) ferritin
Description
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
Time Frame
up to 48 weeks
Title
To assess the safety and tolerability of ascending doses of SP-420
Description
Type and incidence of adverse events (AEs)
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Women and men aged ≥18 years Transfusion-dependent β-thalassemia including HbE/β-thalassemia requiring iron chelation therapy (β-thalassemia with mutation and/or multiplication of α-globin is allowed) On a stable dose of iron chelation for at least 4 weeks prior to screening Weight ≥35 kg at screening 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 Transfusion iron overload defined as LIC ≥5 and ≤20 mg/g dw on the R2-MRI obtained within 2 weeks prior to baseline 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 Willingness to participate and signing the informed consent form Exclusion Criteria: β-thalassemia with the structural Hb variants HbS and HbC Cardiac MRI-T2* score <10 msec obtained within 2 weeks prior to baseline S-ferritin <500 or >4000 ng/mL* 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 Current myelodysplastic syndrome Current biliary disorder ALAT >4 times the upper limit of normal, decompensated cirrhosis, or ascites at screening Past or ongoing history of clinically significant kidney disease Creatinine greater than the upper limit of normal at screening Estimated glomerular filtration rate eGFR <60 mL/min/1.73 m2 Urine protein to creatinine ratio >0.5 mg/mg at screening Heart failure grade II, III and IV by NYHA LVEF on MRI <56 % (echocardiography allowed if MRI not available) 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 Hypertransfused defined as more than 6 units/month in average for the last 6 months prior to screening Ongoing symptoms of neuropathy, including peripheral sensory neuropathy, peripheral motor neuropathy, or paresthesia at screening Platelet count <100×109/L at screening History of hypersensitivity to an iron chelator (investigational or marketed) or excipients Documented history of non-compliance to chelation therapy within past 2 years Received another investigational drug within 30 days or investigational antibody within 90 days before screening 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 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) 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) 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 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pharmacosmos Clinical and non-clinical Department
Phone
+45 5948 5959
Email
info@pharmacosmos.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pharmacosmos Clinical and non-clinical Department
Organizational Affiliation
Pharmacosmos A/S
Official's Role
Study Director
Facility Information:
Facility Name
Pharmacosmos Investigational Site
City
Copenhagen
Country
Denmark
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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A Trial Testing SP-420 in Subjects With Transfusion-dependent β-thalassemia

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