A Trial Testing SP-420 in Subjects With Transfusion-dependent β-thalassemia or Low-risk Myelodysplastic Syndromes

An Open-label, Dose-escalation, Dose-finding, and Proof-of-concept Trial of SP-420 in Subjects With Transfusion-dependent β-thalassemia or Low-risk Myelodysplastic Syndromes

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 or transfusion-dependent low-risk myelodysplastic syndrome.

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 times weekly
• Attend up to 20 site visits
• Undergo MRI scans

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndrome; Beta Thalassemia Major Anemia
• Intervention / Treatment: Drug: SP-420

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pharmacosmos Clinical and non-clinical Department; Phone Number: +45 5948 5959; Email: info@pharmacosmos.com

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Pharmacosmos Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Thalassemia cohorts:

Inclusion criteria:

• Women and men aged 18 years or older
• 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 ≥ 35kg at screening
• Transfusion iron overload
• Treated and followed for at least the past 6 months in a specialized centre

Exclusion criteria:

• β-thalassemia with the structural Hb variants HbS and HbC
• Current MDS
• Current biliary disorder
• Historic or ongoing clinically significant kidney disease
• Unable to undergo trial assessments including MRI e.g. due to claustrophobia in MRI scanner
• Pregnant or nursing women
• Men who do not agree to practice effective barrier contraception during the entire period

Myelodysplastic Syndromes Cohorts:

Inclusion criteria:

• Women and men aged 18 years or older
• Very low, low, or intermediate risk Myelodysplastic Syndrome according to IPSS-R
• Weight ≥ 35kg at screening
• Transfusion iron overload
• Treated and followed for at least the past 6 months at medical facilities experienced with MDS

Exclusion criteria:

• Therapy-related MDS or MDS with a known bone marrow fibrosis
• Diagnosis of decompensated liver cirrhosis
• Clinically significant kidney disease, either historic or ongoing
• Uncontrolled ischemic heart disease or uncontrolled arrythmia
• Uncontrolled hypertension
• Uncontrolled dyslipidaemia
• Uncontrolled Diabetes
• Major surgery within 8 weeks prior to screening
• Pregnant or nursing women
• Men who do not agree to practice effective barrier contraception during the entire period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1a-1b; SP-420 for 48 weeks	Drug: SP-420; Capsules for oral intake
Experimental: Cohort 2a-2b; SP-420 for 48 weeks	Drug: SP-420; Capsules for oral intake
Experimental: Cohort 3a-3b; SP-420 for 48 weeks	Drug: SP-420; Capsules for oral intake
Experimental: 1c-1d; SP-420 for 48 weeks	Drug: SP-420; Capsules for oral intake
Experimental: 2c-2d; SP-420 for 48 weeks	Drug: SP-420; Capsules for oral intake
Experimental: 3c-3d; SP-420 for 48 weeks	Drug: SP-420; Capsules for oral intake

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To establish dose-response relationship of SP-420 for 24 weeks in the treatment of subjects with transfusion-dependent β-thalassemia	24 weeks
To assess the safety and tolerability of ascending doses of SP-420 after 12 weeks treatment of subjects with transfusion-dependent low-risk myelodysplastic syndrome	12 weeks

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	Change in liver iron concentration (LIC) measured by R2-magnetic resonance imaging (MRI) from baseline to week 24	24 weeks
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	12 and 48 weeks
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	up to 48 weeks
To assess the safety and tolerability of ascending doses of SP-420	Type and incidence of adverse events (AEs)	48 weeks

Collaborators and Investigators

• Sponsor: Pharmacosmos A/S
• Collaborators: ICON plc
• Investigators: Study Director: Pharmacosmos Clinical and non-clinical Department, Pharmacosmos A/S

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): May 1, 2028

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 (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 19, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; SP-420
• 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
• product manufactured in and exported from the U.S.: No