Study in Beta-thalassaemia or Myelodysplastic Syndrome Patients to Investigate the Safety and Tolerability of SLN124
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo
|
Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
IMP will be provided as a solution to be injected by qualified clinical staff in patient's abdomen, upper arms or front of the thighs.
|
| Experimental: 0.3 mg/kg
|
Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
IMP will be provided as a solution to be injected by qualified clinical staff in patient's abdomen, upper arms or front of the thighs.
|
| Experimental: 1.0 mg/kg
|
Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
IMP will be provided as a solution to be injected by qualified clinical staff in patient's abdomen, upper arms or front of the thighs.
|
| Experimental: 3.0 mg/kg
|
Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
IMP will be provided as a solution to be injected by qualified clinical staff in patient's abdomen, upper arms or front of the thighs.
|
| Experimental: 10.0 mg/kg
|
Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
IMP will be provided as a solution to be injected by qualified clinical staff in patient's abdomen, upper arms or front of the thighs.
|
Outcome Measures
Primary Outcome Measures
- # 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]
- 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]
- 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
- 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]
Peak Plasma Concentration (Cmax) 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.
Eligibility Criteria
Criteria
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%
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | MHAT Dr. Nikola Vasiliev AD | Kyustendil | Bulgaria | ||
| 2 | UMHAT Dr. Georgi Stranski AD | Pleven | Bulgaria | ||
| 3 | Medical Center COMAC MEDICAL | Sofia | Bulgaria | ||
| 4 | UMHAT Sv. Ivan Rilski | Sofia | Bulgaria | ||
| 5 | Hammersmith Hospital | London | United Kingdom |
Sponsors and Collaborators
- Silence Therapeutics plc
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SLN124-001