Haematological Disorders
Conditions
Interventions
1c1d
2c2d
3c3d
Sponsors
Pharmacosmos AS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Women and men aged =18 years at screening 2. Very low, low, or intermediate risk MDS according to IPSS-R, with an IPSS-R score of =3.5 at screening. An IPSS-R based on an assessment conducted within 6 months prior to screening can be used if the subject is haematologically stable according to the Investigator. An IPSS-R score =2.5 based on an assessment conducted within 12 months prior to screening can be used if the subject is haematologically stable according to the Investigator 3. Required RBC transfusions of =2 units of RBCs due to MDS related anaemia within 16 weeks prior to screening 4. Anticipated to be transfused with at least 6 units of RBCs within the 48 weeks of the trial 5. Weight =35 kg at screening 6. Willing to discontinue any current iron chelation therapy 7 days (± 3 days) prior to the first dose of SP-420 and for the duration of the trial 7. Transfusion iron overload defined as either: a) If no cardiac T2*-MRI is available within the past 6 months prior to screening: S-ferritin >800 ng/mL 2-4 weeks before the screening visit (in medical records) which is confirmed with a second measurement at screening†, and a history of transfusion of 10 to 100 units of RBCs or b) If a cardiac T2*-MRI is available within the past 6 months prior to screening: S-ferritin >800 ng/mL 2-4 weeks before the screening visit (in medical records) which is confirmed with a second measurement at screening†, a history of transfusion of =10 units of RBCs, and a cardiac T2*-MRI score of =25 msec 8. Subject has been treated and followed for at least the past 6 months at medical facilities experienced in MDS, with detailed medical records maintained, including transfusion and iron chelation histories 9. Willingness to participate and signing the ICF †If the Investigator suspects an acute reaction as the cause of the s-ferritin being >800 ng/ml at screening and no suitable data are available from the medical records, a second blood sample may be taken after at least 7 days for re-assessment of eligibility. This will not be considered a re-screening. If the second sample fulfils the enrolment criterion, the subject may be enrolled. The results should be available at the baseline visit at the latest, i.e., max 5 weeks after the screening visit.
Exclusion criteria
Exclusion criteria: 1. Therapy-related MDS or MDS with a known bone marrow fibrosis 2. Any other clinically significant malignancy not remitted or in remission 2.5 times the upper limit of normal (subjects with Gilbert syndrome are exempt from this limit) 8. ALAT or aspartate aminotransferase (ASAT) >3.5 times the upper limit of normal 9. Diagnosis of decompensated liver cirrhosis (either established diagnosis or diagnosis by liver biopsy or appropriate imaging if liver cirrhosis is suspected due to medical history [e.g., hepatitis C virus (HCV) infection] and/or liver function tests) 10. Clinically significant kidney disease, either historic or ongoing 11. eGFR 190 mg/dL (4.9 mmol/L), or triglycerides >500 mg/dL (5.65 mmol/L), or total cholecholesterol/high-density lipoprotein (HDL) cholesterol ratio >5.0) at screening 17. Uncontrolled diabetes (glucose >200 mg/dL (11.1 mmol/L) in presence of typical symptoms of the disease [polyuria, polydipsia, weight loss], or fasting glucose >126 mg/dL (7.0 mmol/L), or recent history of severe hyperglycaemia requiring hospitalisation or emergency medical intervention) at screening 18. A QTcF >450 ms, 2nd or 3rd degree atrioventricular block, complete left bundle branch block, or the presence of clinically significant abnormalities as per Investigator’s judgement at screening 19. Eastern Cooperative Oncology Group (ECOG) performance status >2 20. Life expectancy 40 copies/mL), uncontrolled hepatitis B virus (HBV) infection (defined by HBV DNA =2000 IU/mL), and uncontrolled HCV infection (defined by HCV ribonucleic acid (RNA) >15 IU/mL) 23. Ongoing symptoms of clinically significant neuropathy, including peripheral sensory neuropathy, peripheral
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerability of ascending doses of SP-420 after 12 weeks treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerability of ascending doses of SP-420 ;To assess the efficacy of SP-420 on s-ferritin | — |
Countries
South Africa
Contacts
Public ContactTebogo Mojapelo
Regulatory Scientist
Outcome results
None listed