Description:
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.
Title
- Brief Title: Study in Beta-thalassaemia or Myelodysplastic Syndrome Patients to Investigate the Safety and Tolerability of SLN124
- Official Title: Phase 1b Single Ascending and Multiple Dose First-in-man Study in Adult Patients With Non-transfusion-dependent Beta-thalassaemia or Low Risk Myelodysplastic Syndrome to Investigate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Response of SLN124
Clinical Trial IDs
- ORG STUDY ID:
SLN124-001
- NCT ID:
NCT04176653
Conditions
- Non-transfusion-dependent Thalassemia
- Low Risk Myelodysplastic Syndrome
Interventions
Drug | Synonyms | Arms |
---|
SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo | | 0.3 mg/kg |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Placebo | Placebo Comparator | | - SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
|
0.3 mg/kg | Experimental | | - SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
|
1.0 mg/kg | Experimental | | - SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
|
3.0 mg/kg | Experimental | | - SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
|
10.0 mg/kg | Experimental | | - SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
|
Eligibility 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | # 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 |
Time Frame: | Up to two months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Biomarkers will be measured from baseline to post dose follow up |
Time Frame: | Up to two months |
Safety Issue: | |
Description: | 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. |
Measure: | Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up |
Time Frame: | Up to two months |
Safety Issue: | |
Description: | Peak Plasma Concentration (Cmax) will be analysed by central laboratory. |
Measure: | Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up |
Time Frame: | Up to two months |
Safety Issue: | |
Description: | Area under the plasma concentration versus time curve (AUC) will be analysed by central laboratory. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Withdrawn |
Lead Sponsor: | Silence Therapeutics plc |
Last Updated
April 27, 2020