Study in Beta-thalassaemia or Myelodysplastic Syndrome Patients to Investigate the Safety and Tolerability of SLN124
Phase 1
Withdrawn
- Conditions
- Low Risk Myelodysplastic SyndromeNon-transfusion-dependent Thalassemia
- Interventions
- Registration Number
- NCT04176653
- Lead Sponsor
- Silence Therapeutics plc
- Brief Summary
The primary purpose of this study is to determine the safety and tolerability of SLN124 for the treatment of non-transfusion-dependent (NTD) β-thalassaemia and low risk myelodysplastic syndrome.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria
- Age ≥ 18yrs; BMI 18-35 kg/m2
- β-thalassaemia intermedia or compound heterozygous HbE/β-thalassaemia
- Non-transfusion dependent: ≤ 5 units red cells in last 6 months and transfusion-free for ≥8 weeks
- Hb between 5 & 11 g/dL
- Ferritin > 250 µg/L and /or liver iron ≥ 3mg Fe/g dry weight and TSAT >40%
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Exclusion Criteria
- Haemoglobin S/β-thalassaemia, homozygous β-0 thalassaemia or α thalassaemia
- ALT/AST > 1.5 x upper limit normal or cirrhosis
- eGFR < 60 mL/min/1.73m2
- Platelets <100 or > 1000 x 109/L
- Untreated B12/folate deficiency
- Iron chelation therapy unless stable for ≥8 weeks
- Daily NSAID, therapeutic dose anticoagulant, ESA ≤12 weeks or stable dosing of hydroxyurea ≤ 6 months
- Significant cardiac disease (MI in 6 months, NYHA class III-IV heart failure, long QT)
- HIV or active hepatitis B/C or malignancy within 5 year
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 10.0 mg/kg SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo - 0.3 mg/kg SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo - 1.0 mg/kg SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo - 3.0 mg/kg SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo - Placebo SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo -
- Primary Outcome Measures
Name Time Method clinical chemistry, haematology, urinalysis, liver function tests (included ALT, AST, GGT) will be measured from baseline to post dose follow up Up to two months # of participants with all AEs as assessed by CTCAE V4.0 included injection site reaction, will be measured from baseline to post dose follow up Up to two months 12 lead electrocardiogram parameters included PR, QTcF and QTcB will be measured from baseline to post dose follow up Up to two months height, weight, blood pressure, heart rate, respiration rate and temperature will be measured from baseline to post dose follow up Up to two months
- Secondary Outcome Measures
Name Time Method Biomarkers will be measured from baseline to post dose follow up Up to two months serum hepcidin level (ng/ml), ferritin level (ug/L), Transferrin saturation (%), iron level (umol/L), haemoglobin and reticulocyte count will be analysed by central laboratory.
Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up Up to two months Area under the plasma concentration versus time curve (AUC) will be analysed by central laboratory.
Trial Locations
- Locations (5)
MHAT Dr. Nikola Vasiliev AD
🇧🇬Kyustendil, Bulgaria
Medical Center COMAC MEDICAL
🇧🇬Sofia, Bulgaria
UMHAT Sv. Ivan Rilski
🇧🇬Sofia, Bulgaria
UMHAT Dr. Georgi Stranski AD
🇧🇬Pleven, Bulgaria
Hammersmith Hospital
🇬🇧London, United Kingdom