- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05693909
A Trial Testing SP-420 in Subjects With Transfusion-dependent β-thalassemia
October 18, 2023 updated by: Pharmacosmos A/S
An Open-label, Dose-escalation, Dose-finding, and Proof-of-concept Trial of SP-420 in Subjects With Transfusion-dependent β-thalassemia
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
Study Overview
Study Type
Interventional
Enrollment (Estimated)
90
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Pharmacosmos Clinical and non-clinical Department
- Phone Number: +45 5948 5959
- Email: info@pharmacosmos.com
Study Locations
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Copenhagen, Denmark
- Recruiting
- Pharmacosmos Investigational Site
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Cohort 1
SP-420, 28 mg/kg, three times weekly for 48 weeks
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Capsules for oral intake
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Experimental: Cohort 2
SP-420, 56 mg/kg, three times weekly for 48 weeks
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Capsules for oral intake
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Experimental: Cohort 3
SP-420, 84 mg/kg, three times weekly for 48 weeks
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Capsules for oral intake
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To establish dose-response relationship of SP-420 for 24 weeks in the treatment of subjects with transfusion-dependent β-thalassemia
Time Frame: 24 weeks
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Total body iron removed by SP-420 from baseline to week 24
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24 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To assess the efficacy of SP-420 in clearing iron from the liver after 24 weeks treatment of subjects with transfusion-dependent β-thalassemia
Time Frame: 24 weeks
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Change in liver iron concentration (LIC) measured by R2-magnetic resonance imaging (MRI) from baseline to week 24
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24 weeks
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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
Time Frame: 12 and 48 weeks
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Change in LIC measured by R2-MRI from baseline to week 12 and week 48
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12 and 48 weeks
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To assess the efficacy of SP-420 on serum (s-) ferritin
Time Frame: up to 48 weeks
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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
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up to 48 weeks
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To assess the safety and tolerability of ascending doses of SP-420
Time Frame: 48 weeks
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Type and incidence of adverse events (AEs)
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48 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Pharmacosmos Clinical and non-clinical Department, Pharmacosmos A/S
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 4, 2023
Primary Completion (Estimated)
July 1, 2024
Study Completion (Estimated)
December 1, 2024
Study Registration Dates
First Submitted
December 22, 2022
First Submitted That Met QC Criteria
January 20, 2023
First Posted (Actual)
January 23, 2023
Study Record Updates
Last Update Posted (Actual)
October 23, 2023
Last Update Submitted That Met QC Criteria
October 18, 2023
Last Verified
December 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- P-SP420-THAL-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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