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Trial record 1 of 1 for:    SLN124-002 | MDS | Germany
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A Study Investigate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Response of SLN124 in Adults With Alpha/Beta-thalassaemia and Very Low- and Low-risk Myelodysplastic Syndrome

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ClinicalTrials.gov Identifier: NCT04718844
Recruitment Status : Recruiting
First Posted : January 22, 2021
Last Update Posted : March 15, 2021
Sponsor:
Information provided by (Responsible Party):
Silence Therapeutics plc

Tracking Information
First Submitted Date  ICMJE January 19, 2021
First Posted Date  ICMJE January 22, 2021
Last Update Posted Date March 15, 2021
Estimated Study Start Date  ICMJE March 2021
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 19, 2021)
  • Incidence of treatment-emergent adverse events [ Time Frame: Day 84 ]
    safety and tolerability will be reported separately following single-dose administration.
  • Incidence of treatment-emergent adverse events [ Time Frame: Day 140 ]
    safety and tolerability will be reported separately following multi-dose administration.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2021)
  • Pharmacokinetic: peak plasma concentration (Cmax) [ Time Frame: Day 84 and Day 140 ]
    Will be reported separately following single-dose and multiple-dose administration.
  • Pharmacokinetic: area under the plasma concentration (AUC) [ Time Frame: Day 84 and Day 140 ]
    Will be reported separately following single-dose and multiple-dose administration.
  • Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F) [ Time Frame: Day 84 and Day 140 ]
    Will be reported separately following single-dose and multiple-dose administration.
  • Pharmacodynamic biomarkers: Change in TSAT after s.c injection. [ Time Frame: Day 84 and Day 140 ]
    safety and tolerability will be reported separately following single-dose and multiple-dose administration.
  • Pharmacodynamic biomarkers: Change in hepcidin after s.c injection. [ Time Frame: Day 84 and Day 140 ]
    safety and tolerability will be reported separately following single-dose and multiple-dose administration.
  • Pharmacodynamic biomarkers: Change in serum iron after s.c injection. [ Time Frame: Day 84 and Day 140 ]
    safety and tolerability will be reported separately following single-dose and multiple-dose administration.
  • Pharmacodynamic biomarkers: Change in haemoglobin after s.c injection. [ Time Frame: Day 84 and Day 140 ]
    safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Investigate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Response of SLN124 in Adults With Alpha/Beta-thalassaemia and Very Low- and Low-risk Myelodysplastic Syndrome
Official Title  ICMJE A Randomised, Single-blind, Placebo-controlled, Phase 1, Single-ascending and Multiple-dose Study in Adult Subjects With Alpha/Beta-thalassaemia and Very Low- and Low-risk Myelodysplastic Syndrome to Investigate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Response of SLN124.
Brief Summary This study will investigate the safety and tolerability of SLN124 in patients with Thalassaemia or patients with Very Low- and Low-risk Myelodysplastic Syndrome after single ascending s.c. doses and multiple doses in healthy male and female subjects. Up to 7 cohorts of 56 patients with Thalassaemia and up to 7 cohorts of 56 patients with Myelodysplastic Syndrome will be enrolled. Each subject will receive single or multiple doses of SLN124 or placebo given by subcutaneous (s.c) injection.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-transfusion-dependent Thalassemia
  • Low Risk Myelodysplastic Syndrome
  • Very-Low Risk Myelodysplastic Syndrome
Intervention  ICMJE
  • Drug: SLN124
    SLN124 for subcutaneous (s.c.) injection
  • Drug: Placebo
    Sodium chloride for s.c. injection
Study Arms  ICMJE
  • Experimental: 1.0mg/kg - Thalassaemia
    Intervention: Drug: SLN124
  • Experimental: 3.0mg/kg - Thalassaemia
    Intervention: Drug: SLN124
  • Experimental: 10.0mg/kg - Thalassaemia
    Intervention: Drug: SLN124
  • Placebo Comparator: Placebo - Thalassaemia
    Intervention: Drug: Placebo
  • Experimental: Xmg/kg - Thalassaemia
    Intervention: Drug: SLN124
  • Experimental: 1.0mg/kg - Myelodysplastic Syndrome
    Intervention: Drug: SLN124
  • Experimental: 3.0mg/kg - Myelodysplastic Syndrome
    Intervention: Drug: SLN124
  • Experimental: 10.0mg/kg - Myelodysplastic Syndrome
    Intervention: Drug: SLN124
  • Experimental: Xmg/kg - Myelodysplastic Syndrome
    Intervention: Drug: SLN124
  • Experimental: 3.0mg/kg - Thalassaemia multi dose
    Intervention: Drug: SLN124
  • Experimental: 10.0mg/kg - Thalassaemia multi dose
    Intervention: Drug: SLN124
  • Experimental: Xmg/kg - Thalassaemia multi dose
    Intervention: Drug: SLN124
  • Experimental: 3.0mg/kg - Myelodysplastic Syndrome multi dose
    Intervention: Drug: SLN124
  • Experimental: 10.0mg/kg - Myelodysplastic Syndrome multi dose
    Intervention: Drug: SLN124
  • Experimental: Xmg/kg - Myelodysplastic Syndrome multi dose
    Intervention: Drug: SLN124
  • Placebo Comparator: Placebo - Thalassaemia multi dose
    Intervention: Drug: Placebo
  • Placebo Comparator: Placebo - Myelodysplastic Syndrome
    Intervention: Drug: Placebo
  • Placebo Comparator: Placebo - Myelodysplastic Syndrome multi dose
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 19, 2021)
112
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult with alpha- or beta-thalassaemia or compound heterozygous haemoglobin E/beta-thalassaemia or adult with very low- or low-risk MDS according to the 2016 revision to the World Health Organisation classification.
  • All subjects must agree to adhere to appropriate contraception requirements.
  • Subjects must provide written informed consent and be able to comply with all study requirements.
  • Body mass index ≥18 kg/m2 and ≤35 kg/m2 at screening.
  • At least one of: a) Mean ferritin >250 μg/L based on a minimum of 2 measurements ≥1 week apart within 20 days before the planned dosing day, in the absence of active significant infection; b) Mean TSAT >40% measured on a minimum of 2 occasions ≥1 week apart within 20 days before the planned dosing day; c) Liver iron >3 mg Fe/g dry weight, measured according to local procedures.
  • Mean baseline haemoglobin concentration ≥5 g/dL and ≤11 g/dL, based on a minimum of 2 measurements ≥1 week apart, within 20 days before the planned dosing day.

Exclusion criteria

  • Adult with haemoglobin S/alpha-thalassaemia or haemoglobin S/beta-thalassaemia or adult with secondary MDS, i.e., MDS that is known to have arisen because of chemical injury or treatment with chemotherapy and/or radiation for another disease.
  • History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc, or intolerance to s.c. injections.
  • Known infection with HIV, or active infectious hepatitis A, B, or C virus.
  • Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrolment in the study or could interfere with the subject's participation in, or completion of the study.
  • History or clinical evidence of alcohol or illegal drug misuse within 2 years before screening.
  • Currently using ESA, or plan to use ESA at any point during the study.
  • Require daily treatment with 1 or more non-steroidal anti-inflammatory drugs during the study period. Paracetamol will be permitted for use as an antipyretic and/or analgesic.
  • Treatment, or change in treatment with prohibited medications as specified in the protocol
  • Treatment with ICT where the subject has not been on a stable dose for at least 8 weeks before screening or it is planned to initiate ICT therapy during the study.
  • Clinically significant cardiac disease
  • Clinically significant pulmonary disease

For subjects with thalassaemia:

  • Treatment, or change in treatment with prohibited medications as specified in the protocol
  • currently and anticipated to receiving more than 5 units of RBCs during the 24 weeks to 6 weeks period before first dose of study drug.

For subjects with very low / low-risk MDS:

  • Previous allogeneic or autologous stem cell transplantation.
  • Currently or planned to receive treatment with a corticosteroid for MDS within 8 weeks before screening.
  • Currently or planned to receive treatment with haematopoietic growth factors (e.g., eltrombopag, romiplostim) within 8 weeks before screening.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kristin Greenough +44 20 3934 8038 k.greenough@silence-therapeutics.com
Contact: Annie Woodburne +44 20 3934 8038 a.woodburne@silence-therapeutics.com
Listed Location Countries  ICMJE Germany,   Egypt,   Israel,   Italy,   Jordan,   Lebanon,   Malaysia,   Thailand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04718844
Other Study ID Numbers  ICMJE SLN124-002
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  ICMJE Not Provided
Responsible Party Silence Therapeutics plc
Study Sponsor  ICMJE Silence Therapeutics plc
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Silence Therapeutics plc
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP