Study in Beta-thalassaemia or Myelodysplastic Syndrome Patients to Investigate the Safety and Tolerability of SLN124
Primary Purpose
Non-transfusion-dependent Thalassemia, Low Risk Myelodysplastic Syndrome
Status
Withdrawn
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Non-transfusion-dependent Thalassemia
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
Sites / Locations
- MHAT Dr. Nikola Vasiliev AD
- UMHAT Dr. Georgi Stranski AD
- Medical Center COMAC MEDICAL
- UMHAT Sv. Ivan Rilski
- Hammersmith Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Arm Label
Placebo
0.3 mg/kg
1.0 mg/kg
3.0 mg/kg
10.0 mg/kg
Arm Description
Outcomes
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
12 lead electrocardiogram parameters included PR, QTcF and QTcB will be measured from baseline to post dose follow up
clinical chemistry, haematology, urinalysis, liver function tests (included ALT, AST, GGT) will be measured from baseline to post dose follow up
height, weight, blood pressure, heart rate, respiration rate and temperature will be measured from baseline to post dose follow up
Secondary Outcome Measures
Biomarkers will be measured from baseline to post dose follow up
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
Peak Plasma Concentration (Cmax) will be analysed by central laboratory.
Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up
Area under the plasma concentration versus time curve (AUC) will be analysed by central laboratory.
Full Information
NCT ID
NCT04176653
First Posted
November 7, 2019
Last Updated
April 23, 2020
Sponsor
Silence Therapeutics plc
1. Study Identification
Unique Protocol Identification Number
NCT04176653
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Study stopped prior to subject administered first dose, due to COVID-19
Study Start Date
August 20, 2019 (Actual)
Primary Completion Date
September 30, 2021 (Anticipated)
Study Completion Date
October 14, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Silence Therapeutics plc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-transfusion-dependent Thalassemia, Low Risk Myelodysplastic Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Multiple Group Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
0.3 mg/kg
Arm Type
Experimental
Arm Title
1.0 mg/kg
Arm Type
Experimental
Arm Title
3.0 mg/kg
Arm Type
Experimental
Arm Title
10.0 mg/kg
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
# 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
Title
12 lead electrocardiogram parameters included PR, QTcF and QTcB will be measured from baseline to post dose follow up
Time Frame
Up to two months
Title
clinical chemistry, haematology, urinalysis, liver function tests (included ALT, AST, GGT) will be measured from baseline to post dose follow up
Time Frame
Up to two months
Title
height, weight, blood pressure, heart rate, respiration rate and temperature will be measured from baseline to post dose follow up
Time Frame
Up to two months
Secondary Outcome Measure Information:
Title
Biomarkers will be measured from baseline to post dose follow up
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.
Time Frame
Up to two months
Title
Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up
Description
Peak Plasma Concentration (Cmax) will be analysed by central laboratory.
Time Frame
Up to two months
Title
Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up
Description
Area under the plasma concentration versus time curve (AUC) will be analysed by central laboratory.
Time Frame
Up to two months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
MHAT Dr. Nikola Vasiliev AD
City
Kyustendil
Country
Bulgaria
Facility Name
UMHAT Dr. Georgi Stranski AD
City
Pleven
Country
Bulgaria
Facility Name
Medical Center COMAC MEDICAL
City
Sofia
Country
Bulgaria
Facility Name
UMHAT Sv. Ivan Rilski
City
Sofia
Country
Bulgaria
Facility Name
Hammersmith Hospital
City
London
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study in Beta-thalassaemia or Myelodysplastic Syndrome Patients to Investigate the Safety and Tolerability of SLN124
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