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

NCT04176653 | Withdrawn Phase 1 DMC

• 1 other identifier: SLN124-001
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 5

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.

Conditions

Non-transfusion-dependent Thalassemia; Low Risk Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (4)

• # 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 Outcomes (3)

• Biomarkers will be measured from baseline to post dose follow up

  Up to two months

• Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up

  Up to two months

• Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up

  Up to two months

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo

0.3 mg/kg

EXPERIMENTAL

Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo

1.0 mg/kg

EXPERIMENTAL

Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo

3.0 mg/kg

EXPERIMENTAL

Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo

10.0 mg/kg

EXPERIMENTAL

Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo

Interventions

SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo DRUG

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.

0.3 mg/kg; 1.0 mg/kg; 10.0 mg/kg; 3.0 mg/kg; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Silence Therapeutics plc: lead

Study Sites (5)

MHAT Dr. Nikola Vasiliev AD

Kyustendil, Bulgaria

Location

UMHAT Dr. Georgi Stranski AD

Pleven, Bulgaria

Location

Medical Center COMAC MEDICAL

Sofia, Bulgaria

Location

UMHAT Sv. Ivan Rilski

Sofia, Bulgaria

Location

Hammersmith Hospital

London, United Kingdom

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multiple Group Assignment

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 25, 2019
• Study Start: August 20, 2019
• Primary Completion: September 30, 2021
• Study Completion: October 14, 2021
• Last Updated: April 27, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); BU (4)