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

NCT ID: NCT04718844

Last Updated: 2024-01-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-14
• Study Completion Date: 2023-05-23

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 (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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1.0mg/kg - Thalassaemia

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

3.0mg/kg - Thalassaemia

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

6.0mg/kg - Thalassaemia

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

Placebo - Thalassaemia

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sodium chloride for s.c. injection

Xmg/kg - Thalassaemia

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

1.0mg/kg - Myelodysplastic Syndrome

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

3.0mg/kg - Myelodysplastic Syndrome

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

10.0mg/kg - Myelodysplastic Syndrome

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

Xmg/kg - Myelodysplastic Syndrome

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

3.0mg/kg - Thalassaemia multi dose

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

10.0mg/kg - Thalassaemia multi dose

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

Xmg/kg - Thalassaemia multi dose

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

3.0mg/kg - Myelodysplastic Syndrome multi dose

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

10.0mg/kg - Myelodysplastic Syndrome multi dose

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

Xmg/kg - Myelodysplastic Syndrome multi dose

Group Type: EXPERIMENTAL

SLN124

Intervention Type: DRUG

SLN124 for subcutaneous (s.c.) injection

Placebo - Thalassaemia multi dose

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sodium chloride for s.c. injection

Placebo - Myelodysplastic Syndrome

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sodium chloride for s.c. injection

Placebo - Myelodysplastic Syndrome multi dose

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sodium chloride for s.c. injection

Interventions

SLN124

SLN124 for subcutaneous (s.c.) injection

Intervention Type: DRUG

Placebo

Sodium chloride for s.c. injection

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Silence Therapeutics plc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Universitaetsklinikum Duesseldorf

Düsseldorf, , Germany

Universitat Leipzig

Leipzig, , Germany

Rambam Health Care Campus

Haifa, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Bar-Ilan University - Faculty of Medicine

Safed, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

AUSL della Romagna - Ospedale di Ravenna

Ravenna, , Italy

Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia

Reggio Emilia, , Italy

Jordan University Hospital

Amman, , Jordan

King Hussein Cancer Center

Amman, , Jordan

Irbid Speciality Hospital

Irbid, , Jordan

Sarawak General Hospital

Kampung Sarawak, , Malaysia

Hospital Ampang

Kampung Selangor, , Malaysia

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Mahidol University - Faculty of Medicine - Ramathibodi Hospital

Bangkok, , Thailand

Mahidol University - Siriraj Hospital

Bangkok, , Thailand

Faculty of Medicine, Chiang Mai University

Chiang Mai, , Thailand

University Hospital of Wales

Cardiff, , United Kingdom

The Leeds Teaching Hospitals NHS Trust - Saint James's University Hospital

Leeds, , United Kingdom

Hammersmith Medicines Research Ltd (HMR)

London, , United Kingdom

Countries

Germany; Israel; Italy; Jordan; Malaysia; Thailand; United Kingdom

Other Identifiers

SLN124-002

Identifier Type: -

Identifier Source: org_study_id