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
- Conditions
- Non-transfusion-dependent ThalassemiaLow Risk Myelodysplastic SyndromeVery-Low Risk Myelodysplastic Syndrome
- Interventions
- Drug: PlaceboDrug: SLN124
- Registration Number
- NCT04718844
- Lead Sponsor
- Silence Therapeutics plc
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 44
- 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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo - Myelodysplastic Syndrome Placebo - 10.0mg/kg - Thalassaemia multi dose SLN124 - 1.0mg/kg - Thalassaemia SLN124 - 3.0mg/kg - Thalassaemia SLN124 - 6.0mg/kg - Thalassaemia SLN124 - Placebo - Thalassaemia Placebo - Xmg/kg - Thalassaemia SLN124 - 1.0mg/kg - Myelodysplastic Syndrome SLN124 - 3.0mg/kg - Myelodysplastic Syndrome SLN124 - 10.0mg/kg - Myelodysplastic Syndrome SLN124 - Xmg/kg - Myelodysplastic Syndrome SLN124 - Xmg/kg - Thalassaemia multi dose SLN124 - 3.0mg/kg - Myelodysplastic Syndrome multi dose SLN124 - 10.0mg/kg - Myelodysplastic Syndrome multi dose SLN124 - Xmg/kg - Myelodysplastic Syndrome multi dose SLN124 - Placebo - Thalassaemia multi dose Placebo - Placebo - Myelodysplastic Syndrome multi dose Placebo - 3.0mg/kg - Thalassaemia multi dose SLN124 -
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events Day 140 safety and tolerability will be reported separately following multi-dose administration.
- Secondary Outcome Measures
Name Time Method Pharmacokinetic: area under the plasma concentration (AUC) 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) Day 84 and Day 140 Will be reported separately following single-dose and multiple-dose administration.
Pharmacokinetic: peak plasma concentration (Cmax) 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. 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. 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. 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. Day 84 and Day 140 safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Trial Locations
- Locations (20)
Sarawak General Hospital
🇲🇾Kampung Sarawak, Malaysia
King Chulalongkorn Memorial Hospital
🇹🇭Bangkok, Thailand
Mahidol University - Faculty of Medicine - Ramathibodi Hospital
🇹🇭Bangkok, Thailand
Hospital Ampang
🇲🇾Kampung Selangor, Malaysia
Universitaetsklinikum Duesseldorf
🇩🇪Düsseldorf, Germany
Universitat Leipzig
🇩🇪Leipzig, Germany
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Jordan University Hospital
🇯🇴Amman, Jordan
King Hussein Cancer Center
🇯🇴Amman, Jordan
Irbid Speciality Hospital
🇯🇴Irbid, Jordan
AUSL della Romagna - Ospedale di Ravenna
🇮🇹Ravenna, Italy
Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia
🇮🇹Reggio Emilia, Italy
Bar-Ilan University - Faculty of Medicine
🇮🇱Zefat, Israel
Hammersmith Medicines Research Ltd (HMR)
🇬🇧London, United Kingdom
Mahidol University - Siriraj Hospital
🇹🇭Bangkok, Thailand
The Leeds Teaching Hospitals NHS Trust - Saint James's University Hospital
🇬🇧Leeds, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Faculty of Medicine, Chiang Mai University
🇹🇭Chiang Mai, Thailand
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Rambam Health Care Campus
🇮🇱Haifa, Israel