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

Non-transfusion-dependent Thalassemia Clinical Trial

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Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04176653
• Other study ID #: SLN124-001
• Status: Withdrawn
• Phase: Phase 1
• Start date: August 20, 2019
• Est. completion date: October 14, 2021

Study information

• Verified date: April 2020
• Source: Silence Therapeutics plc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 14, 2021
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18yrs; BMI 18-35 kg/m2

• ß-thalassaemia intermedia or compound heterozygous HbE/ß-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/ß-thalassaemia, homozygous ß-0 thalassaemia or a 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

Related Conditions & MeSH terms

• beta-Thalassemia
• Low Risk Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Non-transfusion-dependent Thalassemia
• Preleukemia
• Syndrome
• Thalassemia

Intervention

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.

Locations

Country	Name	City	State
Bulgaria	MHAT Dr. Nikola Vasiliev AD	Kyustendil
Bulgaria	UMHAT Dr. Georgi Stranski AD	Pleven
Bulgaria	Medical Center COMAC MEDICAL	Sofia
Bulgaria	UMHAT Sv. Ivan Rilski	Sofia
United Kingdom	Hammersmith Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Silence Therapeutics plc

Countries where clinical trial is conducted

Bulgaria,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	# 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
Primary	12 lead electrocardiogram parameters included PR, QTcF and QTcB will be measured from baseline to post dose follow up		Up to two months
Primary	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
Primary	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	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.	Up to two months
Secondary	Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up	Peak Plasma Concentration (Cmax) will be analysed by central laboratory.	Up to two months
Secondary	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.	Up to two months