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

January 2, 2024 updated by: Silence Therapeutics plc

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.

This study will investigate the safety and tolerability of SLN124 in patients with Thalassaemia or patients with Very Low- and Low-risk Myelodysplastic Syndrome (MDS) 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 MDS will be enrolled. Each subject will receive single or multiple doses of SLN124 or placebo given by subcutaneous (s.c) injection.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
44

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Germany
      • Düsseldorf, Germany
        • Universitaetsklinikum Duesseldorf
      • Leipzig, Germany
        • Universität Leipzig
  • Israel
      • Haifa, Israel
        • Rambam Health Care Campus
      • Ramat Gan, Israel
        • Sheba Medical Center
      • Tel Aviv, Israel
        • Tel Aviv Sourasky Medical Center
      • Zefat, Israel
        • Bar-Ilan University - Faculty of Medicine
  • Italy
      • Ravenna, Italy
        • AUSL della Romagna - Ospedale di Ravenna
      • Reggio Emilia, Italy
        • Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia
  • Jordan
      • Amman, Jordan
        • Jordan University Hospital
      • Amman, Jordan
        • King Hussein Cancer Center
      • Irbid, Jordan
        • Irbid Speciality Hospital
  • Malaysia
      • Kampung Sarawak, Malaysia
        • Sarawak General Hospital
      • Kampung Selangor, Malaysia
        • Hospital Ampang
  • Thailand
      • Bangkok, Thailand
        • King Chulalongkorn Memorial Hospital
      • Bangkok, Thailand
        • Mahidol University - Faculty of Medicine - Ramathibodi Hospital
      • Bangkok, Thailand
        • Mahidol University - Siriraj Hospital
      • Chiang Mai, Thailand
        • Faculty of Medicine, Chiang Mai University
  • United Kingdom
      • Cardiff, United Kingdom
        • University Hospital of Wales
      • Leeds, United Kingdom
        • The Leeds Teaching Hospitals NHS Trust - Saint James's University Hospital
      • London, United Kingdom
        • Hammersmith Medicines Research Ltd (HMR)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of treatment-emergent adverse events
Time Frame: Day 84
safety and tolerability will be reported separately following single-dose administration.
Day 84
Incidence of treatment-emergent adverse events
Time Frame: Day 140
safety and tolerability will be reported separately following multi-dose administration.
Day 140

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetic: peak plasma concentration (Cmax)
Time Frame: Day 84 and Day 140
Will be reported separately following single-dose and multiple-dose administration.
Day 84 and Day 140
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.
Day 84 and Day 140
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.
Day 84 and Day 140
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.
Day 84 and Day 140
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.
Day 84 and Day 140
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.
Day 84 and Day 140
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.
Day 84 and Day 140

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Silence Therapeutics plc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 14, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 23, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 23, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 19, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 22, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 3, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 2, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SLN124-002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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