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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Non-transfusion-dependent Thalassemia; Low Risk Myelodysplastic Syndrome
• Intervention / Treatment: Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	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.
Experimental: 0.3 mg/kg	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.
Experimental: 1.0 mg/kg	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.
Experimental: 3.0 mg/kg	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.
Experimental: 10.0 mg/kg	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
# 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
12 lead electrocardiogram parameters included PR, QTcF and QTcB will be measured from baseline to post dose follow up	Up to two months
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Silence Therapeutics plc

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2019
• Primary Completion (Anticipated): September 30, 2021
• Study Completion (Anticipated): October 14, 2021

Study Registration Dates

• First Submitted: November 7, 2019
• First Submitted That Met QC Criteria: November 21, 2019
• First Posted (Actual): November 25, 2019

Study Record Updates

• Last Update Posted (Actual): April 27, 2020
• Last Update Submitted That Met QC Criteria: April 23, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Precancerous Conditions; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Syndrome; Myelodysplastic Syndromes; Preleukemia; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: SLN124-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No