Study in Beta-thalassaemia or Myelodysplastic Syndrome Patients to Investigate the Safety and Tolerability of SLN124

Silence Therapeutics

Status and phase: Withdrawn; Phase 1

Conditions: Non-transfusion-dependent Thalassemia; Low Risk Myelodysplastic Syndrome

Treatments: Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04176653

SLN124-001

Details and patient eligibility

About

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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0 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Drug: 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 group

Treatment:

Drug: 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 group

Treatment:

Drug: 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 group

Treatment:

Drug: 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 group

Treatment:

Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo