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

NCT04718844 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: SLN124-002
• Study Type: interventional
• Target: 44
• Locations: 7 countries
• Sites: 20

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

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-emergent adverse events

  safety and tolerability will be reported separately following single-dose administration.

  Day 84

• Incidence of treatment-emergent adverse events

  safety and tolerability will be reported separately following multi-dose administration.

  Day 140

Secondary Outcomes (7)

• Pharmacokinetic: peak plasma concentration (Cmax)

  Day 84 and Day 140

• Pharmacokinetic: area under the plasma concentration (AUC)

  Day 84 and Day 140

• Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F)

  Day 84 and Day 140

• Pharmacodynamic biomarkers: Change in TSAT after s.c injection.

  Day 84 and Day 140

• Pharmacodynamic biomarkers: Change in hepcidin after s.c injection.

  Day 84 and Day 140

Study Arms (18)

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

Interventions

SLN124 DRUG

SLN124 for subcutaneous (s.c.) injection

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

Placebo DRUG

Sodium chloride for s.c. injection

Placebo - Myelodysplastic Syndrome; Placebo - Myelodysplastic Syndrome multi dose; Placebo - Thalassaemia; Placebo - Thalassaemia multi dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• Silence Therapeutics plc: lead

Study Sites (20)

Universitaetsklinikum Duesseldorf

Düsseldorf, Germany

Location

Universitat Leipzig

Leipzig, Germany

Location

Rambam Health Care Campus

Haifa, Israel

Location

Sheba Medical Center

Ramat Gan, Israel

Location

Bar-Ilan University - Faculty of Medicine

Safed, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

AUSL della Romagna - Ospedale di Ravenna

Ravenna, Italy

Location

Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia

Reggio Emilia, Italy

Location

Jordan University Hospital

Amman, Jordan

Location

King Hussein Cancer Center

Amman, Jordan

Location

Irbid Speciality Hospital

Irbid, Jordan

Location

Sarawak General Hospital

Kampung Sarawak, Malaysia

Location

Hospital Ampang

Kampung Selangor, Malaysia

Location

King Chulalongkorn Memorial Hospital

Bangkok, Thailand

Location

Mahidol University - Faculty of Medicine - Ramathibodi Hospital

Bangkok, Thailand

Location

Mahidol University - Siriraj Hospital

Bangkok, Thailand

Location

Faculty of Medicine, Chiang Mai University

Chiang Mai, Thailand

Location

University Hospital of Wales

Cardiff, United Kingdom

Location

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

Leeds, United Kingdom

Location

Hammersmith Medicines Research Ltd (HMR)

London, United Kingdom

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: January 22, 2021
• Study Start: April 14, 2021
• Primary Completion: May 23, 2023
• Study Completion: May 23, 2023
• Last Updated: January 3, 2024

Record last verified: 2024-01

Locations

GB (3); IL (4); IT (2); JO (3); DE (2); MY (2); TH (4)