Clinical Trials /

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

NCT04176653

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.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Withdrawn

Phase:

Phase 1

Trial Eligibility

Document

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

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

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

NameTypeDescriptionInterventions
PlaceboPlacebo Comparator
  • SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
0.3 mg/kgExperimental
  • SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
1.0 mg/kgExperimental
  • SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
3.0 mg/kgExperimental
  • SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
10.0 mg/kgExperimental
  • 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:Recruiting
Lead Sponsor:Silence Therapeutics plc

Last Updated

November 21, 2019