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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Withdrawn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

About this trial

This is an interventional treatment trial for Non-transfusion-dependent Thalassemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

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

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

Studies a U.S. FDA-regulated Device Product

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

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

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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