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

• ClinicalTrials.gov Identifier: NCT04176653
• Recruitment Status: Withdrawn
• First Posted: November 25, 2019
• Last Update Posted: April 27, 2020
• Sponsor: Silence Therapeutics plc
• Information provided by (Responsible Party): Silence Therapeutics plc

Tracking Information

• First Submitted Date: November 7, 2019
• First Posted Date: November 25, 2019
• Last Update Posted Date: April 27, 2020
• Actual Study Start Date: August 20, 2019
• Estimated Primary Completion Date: September 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 21, 2019)

• # 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 ]
• 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 ]
• 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 ]
• 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 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 21, 2019)

• Biomarkers will be measured from baseline to post dose follow up [ Time Frame: Up to two months ]
  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 [ Time Frame: Up to two months ]
  Peak Plasma Concentration (Cmax) will be analysed by central laboratory.
• Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up [ Time Frame: Up to two months ]
  Area under the plasma concentration versus time curve (AUC) will be analysed by central laboratory.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Multiple Group Assignment

Masking: Double (Participant, Investigator)
Primary Purpose: Treatment

Condition

• Non-transfusion-dependent Thalassemia
• Low Risk Myelodysplastic Syndrome

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.

Study Arms

• Placebo Comparator: Placebo
  Intervention: Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
• Experimental: 0.3 mg/kg
  Intervention: Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
• Experimental: 1.0 mg/kg
  Intervention: Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
• Experimental: 3.0 mg/kg
  Intervention: Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
• Experimental: 10.0 mg/kg
  Intervention: Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: April 23, 2020): 0
• Original Estimated Enrollment (submitted: November 21, 2019): 70
• Estimated Study Completion Date: October 14, 2021
• Estimated Primary Completion Date: September 30, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, United Kingdom

Administrative Information

• NCT Number: NCT04176653
• Other Study ID Numbers: SLN124-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Silence Therapeutics plc
• Original Responsible Party: Same as current
• Current Study Sponsor: Silence Therapeutics plc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Silence Therapeutics plc
• Verification Date: April 2020