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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04176653
Recruitment Status : Recruiting
First Posted : November 25, 2019
Last Update Posted : November 25, 2019
Sponsor:
Information provided by (Responsible Party):
Silence Therapeutics plc

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.

Condition or disease Intervention/treatment Phase
Non-transfusion-dependent Thalassemia Low Risk Myelodysplastic Syndrome Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multiple Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : August 20, 2019
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : October 14, 2021


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.




Primary Outcome Measures :
  1. # 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 Measures :
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04176653


Contacts
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Contact: Go Matsumura +442034576900 ext 6895 g.matsumura@silence-therapeutics.com

Locations
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Bulgaria
MHAT Dr. Nikola Vasiliev AD Recruiting
Kyustendil, Bulgaria
UMHAT Dr. Georgi Stranski AD Recruiting
Pleven, Bulgaria
Medical Center COMAC MEDICAL Not yet recruiting
Sofia, Bulgaria
UMHAT Sv. Ivan Rilski Recruiting
Sofia, Bulgaria
United Kingdom
Hammersmith Hospital Recruiting
London, United Kingdom
Sponsors and Collaborators
Silence Therapeutics plc

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Responsible Party: Silence Therapeutics plc
ClinicalTrials.gov Identifier: NCT04176653    
Other Study ID Numbers: SLN124-001
First Posted: November 25, 2019    Key Record Dates
Last Update Posted: November 25, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Thalassemia
beta-Thalassemia
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hemoglobinopathies
Genetic Diseases, Inborn