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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

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: NCT04718844
Recruitment Status : Recruiting
First Posted : January 22, 2021
Last Update Posted : April 1, 2022
Sponsor:
Information provided by (Responsible Party):
Silence Therapeutics plc

Study Description
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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.

Condition or disease Intervention/treatment Phase
Non-transfusion-dependent Thalassemia Low Risk Myelodysplastic Syndrome Very-Low Risk Myelodysplastic Syndrome Drug: SLN124 Drug: Placebo Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : April 14, 2021
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 1.0mg/kg - Thalassaemia Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Experimental: 3.0mg/kg - Thalassaemia Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Experimental: 6.0mg/kg - Thalassaemia Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Placebo Comparator: Placebo - Thalassaemia Drug: Placebo
Sodium chloride for s.c. injection
Experimental: Xmg/kg - Thalassaemia Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Experimental: 1.0mg/kg - Myelodysplastic Syndrome Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Experimental: 3.0mg/kg - Myelodysplastic Syndrome Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Experimental: 10.0mg/kg - Myelodysplastic Syndrome Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Experimental: Xmg/kg - Myelodysplastic Syndrome Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Experimental: 3.0mg/kg - Thalassaemia multi dose Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Experimental: 10.0mg/kg - Thalassaemia multi dose Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Experimental: Xmg/kg - Thalassaemia multi dose Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Experimental: 3.0mg/kg - Myelodysplastic Syndrome multi dose Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Experimental: 10.0mg/kg - Myelodysplastic Syndrome multi dose Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Experimental: Xmg/kg - Myelodysplastic Syndrome multi dose Drug: SLN124
SLN124 for subcutaneous (s.c.) injection
Placebo Comparator: Placebo - Thalassaemia multi dose Drug: Placebo
Sodium chloride for s.c. injection
Placebo Comparator: Placebo - Myelodysplastic Syndrome Drug: Placebo
Sodium chloride for s.c. injection
Placebo Comparator: Placebo - Myelodysplastic Syndrome multi dose Drug: Placebo
Sodium chloride for s.c. injection


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events [ Time Frame: Day 84 ]
    safety and tolerability will be reported separately following single-dose administration.

  2. Incidence of treatment-emergent adverse events [ Time Frame: Day 140 ]
    safety and tolerability will be reported separately following multi-dose administration.


Secondary Outcome Measures :
  1. Pharmacokinetic: peak plasma concentration (Cmax) [ Time Frame: Day 84 and Day 140 ]
    Will be reported separately following single-dose and multiple-dose administration.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.


Eligibility Criteria
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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:

  • 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.
Contacts and Locations
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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): NCT04718844


Contacts
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Contact: Kristin Greenough +44 20 3934 8038 k.greenough@silence-therapeutics.com
Contact: Elena Townson +44 20 3934 8038 e.townson@silence-therapeutics.com

Locations
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Sponsors and Collaborators
Silence Therapeutics plc
More Information
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Responsible Party: Silence Therapeutics plc
ClinicalTrials.gov Identifier: NCT04718844    
Other Study ID Numbers: SLN124-002
First Posted: January 22, 2021    Key Record Dates
Last Update Posted: April 1, 2022
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
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