Non-transfusion-dependent ThalassemiaPhase 1NCT04718844

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

A Phase 1 study testing SLN124 in people with Non-transfusion-dependent Thalassemia and Low Risk Myelodysplastic Syndrome, run by Silence Therapeutics plc at 20 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Non-transfusion-dependent Thalassemia, Low Risk Myelodysplastic Syndrome, Very-Low Risk Myelodysplastic Syndrome
What is being tested?: SLN124
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 44 participants
Where: 20 sitesin 7 countries
Study dates: 14 Apr 2021to 23 May 2023
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 18Show fewer

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.

Trial locations and contacts

20 sites in 7 countries.

Country

City, postcode or hospital

20 sites in 7 countries

Israel4 sites

Rambam Health Care Campus
Haifa
Sheba Medical Center
Ramat Gan
Bar-Ilan University - Faculty of Medicine
Safed
Tel Aviv Sourasky Medical Center
Tel Aviv

Other trials in Israel

Thailand4 sites

King Chulalongkorn Memorial Hospital
Bangkok
Mahidol University - Faculty of Medicine - Ramathibodi Hospital
Bangkok
Mahidol University - Siriraj Hospital
Bangkok
Faculty of Medicine, Chiang Mai University
Chiang Mai

Other trials in Thailand

Jordan3 sites

Jordan University Hospital
Amman
King Hussein Cancer Center
Amman
Irbid Speciality Hospital
Irbid

Other trials in Jordan

United Kingdom3 sites

University Hospital of Wales
Cardiff
The Leeds Teaching Hospitals NHS Trust - Saint James's University Hospital
Leeds
Hammersmith Medicines Research Ltd (HMR)
London

Other trials in United Kingdom

Germany2 sites

Universitaetsklinikum Duesseldorf
Düsseldorf
Universitat Leipzig
Leipzig

Other trials in Germany

Italy2 sites

AUSL della Romagna - Ospedale di Ravenna
Ravenna
Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia
Reggio Emilia

Other trials in Italy

Malaysia2 sites

Sarawak General Hospital
Kampung Sarawak
Hospital Ampang
Kampung Selangor

Other trials in Malaysia

About this study

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.

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.

Conditions: Non-transfusion-dependent Thalassemia, Low Risk Myelodysplastic Syndrome, Very-Low Risk Myelodysplastic Syndrome
Being tested: SLN124, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SLN124Drug
SLN124 for subcutaneous (s.c.) injection
PlaceboDrug
Sodium chloride for s.c. injection

Study groups in NCT04718844
Study group	Role	What they receive
1.0mg/kg - Thalassaemia	Experimental	Not described Receives: Drug: SLN124
3.0mg/kg - Thalassaemia	Experimental	Not described Receives: Drug: SLN124
6.0mg/kg - Thalassaemia	Experimental	Not described Receives: Drug: SLN124
Placebo - Thalassaemia	Placebo comparator	Not described Receives: Drug: Placebo
Xmg/kg - Thalassaemia	Experimental	Not described Receives: Drug: SLN124
1.0mg/kg - Myelodysplastic Syndrome	Experimental	Not described Receives: Drug: SLN124
3.0mg/kg - Myelodysplastic Syndrome	Experimental	Not described Receives: Drug: SLN124
10.0mg/kg - Myelodysplastic Syndrome	Experimental	Not described Receives: Drug: SLN124
Xmg/kg - Myelodysplastic Syndrome	Experimental	Not described Receives: Drug: SLN124
3.0mg/kg - Thalassaemia multi dose	Experimental	Not described Receives: Drug: SLN124
10.0mg/kg - Thalassaemia multi dose	Experimental	Not described Receives: Drug: SLN124
Xmg/kg - Thalassaemia multi dose	Experimental	Not described Receives: Drug: SLN124
3.0mg/kg - Myelodysplastic Syndrome multi dose	Experimental	Not described Receives: Drug: SLN124
10.0mg/kg - Myelodysplastic Syndrome multi dose	Experimental	Not described Receives: Drug: SLN124
Xmg/kg - Myelodysplastic Syndrome multi dose	Experimental	Not described Receives: Drug: SLN124
Placebo - Thalassaemia multi dose	Placebo comparator	Not described Receives: Drug: Placebo
Placebo - Myelodysplastic Syndrome	Placebo comparator	Not described Receives: Drug: Placebo
Placebo - Myelodysplastic Syndrome multi dose	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of treatment-emergent adverse events
safety and tolerability will be reported separately following single-dose administration.
Measured: Day 84
Incidence of treatment-emergent adverse events
safety and tolerability will be reported separately following multi-dose administration.
Measured: Day 140

Secondary outcomes (7)

Pharmacokinetic: peak plasma concentration (Cmax)
Will be reported separately following single-dose and multiple-dose administration.
Measured: Day 84 and Day 140
Pharmacokinetic: area under the plasma concentration (AUC)
Will be reported separately following single-dose and multiple-dose administration.
Measured: Day 84 and Day 140
Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F)
Will be reported separately following single-dose and multiple-dose administration.
Measured: Day 84 and Day 140
Pharmacodynamic biomarkers: Change in TSAT after s.c injection.
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Measured: Day 84 and Day 140
Pharmacodynamic biomarkers: Change in hepcidin after s.c injection.
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Measured: Day 84 and Day 140
Pharmacodynamic biomarkers: Change in serum iron after s.c injection.
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Measured: Day 84 and Day 140
Pharmacodynamic biomarkers: Change in haemoglobin after s.c injection.
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Measured: Day 84 and Day 140

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Apr 202123 May 2023

First posted22 Jan 2021
Study start14 Apr 2021
Primary completion23 May 2023
Study completion23 May 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Non-transfusion-dependent ThalassemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04718844
Sponsor's protocol ID: SLN124-002
Status last verified: Jan 2024
First submitted: 19 Jan 2021
Last updated: 3 Jan 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 3
A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)
Non-Transfusion-dependent Alpha-Thalassemia, Non-Transfusion-dependent Beta-Thalassemia
RecruitingPhase 3
A Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Participants With α- or β-Non-Transfusion-Dependent Thalassemia
Non-Transfusion-dependent Alpha-Thalassemia, Non-Transfusion-dependent Beta-Thalassemia
Active, not recruitingPhase 2
A Study to Determine the Efficacy and Safety of Luspatercept in Adult Participants and to Evaluate the Safety and Pharmacokinetics in and Adolescent Participants With Alpha (α)-Thalassemia
Anemia
RecruitingObservational study
A Real-World Study to Evaluate Luspatercept in Adults With Transfusion-Dependent Beta-Thalassemia in the Middle East
β-thalassemia
Active, not recruitingPhase 2
A Study to Test the Safety, Tolerability, and Efficacy of an Antibody, REGN7999, Injected Under the Skin for the Treatment of Iron Overload in Adult Participants With Non-Transfusion Dependent β-thalassemia, Using MRI Scans to Measure Iron Levels in the Body
Non-Transfusion Dependent Beta-Thalassemia (NTDT)

All Non-transfusion-dependent Thalassemia trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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.
ClinicalTrials.gov ID: NCT04718844
Acronym / sponsor ID: SLN124-002
Conditions: Non-transfusion-dependent Thalassemia, Low Risk Myelodysplastic Syndrome, Very-Low Risk Myelodysplastic Syndrome
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 44 participants (actual)
Lead sponsor: Silence Therapeutics plcIndustry (pharma, biotech, devices)
Study start: 14 Apr 2021 (actual)
Primary completion: 23 May 2023 (actual)
Study completion: 23 May 2023 (actual)
First posted: 22 Jan 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 18

Arm	Type	Receives
1.0mg/kg - Thalassaemia	Experimental	Drug: SLN124
3.0mg/kg - Thalassaemia	Experimental	Drug: SLN124
6.0mg/kg - Thalassaemia	Experimental	Drug: SLN124
Placebo - Thalassaemia	Placebo comparator	Drug: Placebo
Xmg/kg - Thalassaemia	Experimental	Drug: SLN124
1.0mg/kg - Myelodysplastic Syndrome	Experimental	Drug: SLN124
3.0mg/kg - Myelodysplastic Syndrome	Experimental	Drug: SLN124
10.0mg/kg - Myelodysplastic Syndrome	Experimental	Drug: SLN124
Xmg/kg - Myelodysplastic Syndrome	Experimental	Drug: SLN124
3.0mg/kg - Thalassaemia multi dose	Experimental	Drug: SLN124
10.0mg/kg - Thalassaemia multi dose	Experimental	Drug: SLN124
Xmg/kg - Thalassaemia multi dose	Experimental	Drug: SLN124
3.0mg/kg - Myelodysplastic Syndrome multi dose	Experimental	Drug: SLN124
10.0mg/kg - Myelodysplastic Syndrome multi dose	Experimental	Drug: SLN124
Xmg/kg - Myelodysplastic Syndrome multi dose	Experimental	Drug: SLN124
Placebo - Thalassaemia multi dose	Placebo comparator	Drug: Placebo
Placebo - Myelodysplastic Syndrome	Placebo comparator	Drug: Placebo
Placebo - Myelodysplastic Syndrome multi dose	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (18 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SLN124SLN124 for subcutaneous (s.c.) injection	Drug	1.0mg/kg - Myelodysplastic Syndrome, 1.0mg/kg - Thalassaemia, 10.0mg/kg - Myelodysplastic Syndrome, 10.0mg/kg - Myelodysplastic Syndrome multi dose, 10.0mg/kg - Thalassaemia multi dose, 3.0mg/kg - Myelodysplastic Syndrome, 3.0mg/kg - Myelodysplastic Syndrome multi dose, 3.0mg/kg - Thalassaemia, 3.0mg/kg - Thalassaemia multi dose, 6.0mg/kg - Thalassaemia, Xmg/kg - Myelodysplastic Syndrome, Xmg/kg - Myelodysplastic Syndrome multi dose, Xmg/kg - Thalassaemia, Xmg/kg - Thalassaemia multi dose
PlaceboSodium chloride for s.c. injection	Drug	Placebo - Myelodysplastic Syndrome, Placebo - Myelodysplastic Syndrome multi dose, Placebo - Thalassaemia, Placebo - Thalassaemia multi dose

Primary outcome

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.

7 secondary outcomes

Pharmacokinetic: peak plasma concentration (Cmax)
Time frame: Day 84 and Day 140
Pharmacokinetic: area under the plasma concentration (AUC)
Time frame: Day 84 and Day 140
Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F)
Time frame: Day 84 and Day 140
Pharmacodynamic biomarkers: Change in TSAT after s.c injection.
Time frame: Day 84 and Day 140
Pharmacodynamic biomarkers: Change in hepcidin after s.c injection.
Time frame: Day 84 and Day 140
Pharmacodynamic biomarkers: Change in serum iron after s.c injection.
Time frame: Day 84 and Day 140
Pharmacodynamic biomarkers: Change in haemoglobin after s.c injection.
Time frame: Day 84 and Day 140

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2024.

Related trials for Non-transfusion-dependent Thalassemia

Active, not recruitingPhase 3
A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)
Non-Transfusion-dependent Alpha-Thalassemia, Non-Transfusion-dependent Beta-Thalassemia
RecruitingPhase 3
A Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Participants With α- or β-Non-Transfusion-Dependent Thalassemia
Non-Transfusion-dependent Alpha-Thalassemia, Non-Transfusion-dependent Beta-Thalassemia
Active, not recruitingPhase 2
A Study to Determine the Efficacy and Safety of Luspatercept in Adult Participants and to Evaluate the Safety and Pharmacokinetics in and Adolescent Participants With Alpha (α)-Thalassemia
Anemia
RecruitingObservational study
A Real-World Study to Evaluate Luspatercept in Adults With Transfusion-Dependent Beta-Thalassemia in the Middle East
β-thalassemia
Active, not recruitingPhase 2
A Study to Test the Safety, Tolerability, and Efficacy of an Antibody, REGN7999, Injected Under the Skin for the Treatment of Iron Overload in Adult Participants With Non-Transfusion Dependent β-thalassemia, Using MRI Scans to Measure Iron Levels in the Body
Non-Transfusion Dependent Beta-Thalassemia (NTDT)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

20 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SLN124 in people with Non-transfusion-dependent Thalassemia and Low Risk Myelodysplastic Syndrome, run by Silence Therapeutics plc at 20 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Israel, Thailand, Jordan, United Kingdom, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of treatment-emergent adverse events (time frame: Day 84). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04718844.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2024.