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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04718844

Studienbeginn:
März 2021

Letztes Update:
15.03.2021

Wirkstoff:
SLN124, Placebo

Indikation (Clinical Trials):
Preleukemia, Myelodysplastic Syndromes, Thalassemia, beta-Thalassemia, Syndrome

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Silence Therapeutics plc

Collaborator:
-

Kontakt

Studienlocations
(3 von 14)

Germany
Düsseldorf
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
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Studien-Informationen

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 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 Myelodysplastic

Syndrome will be enrolled. Each subject will receive single or multiple doses of SLN124 or

placebo given by subcutaneous (s.c) injection.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. Incidence of treatment-emergent adverse events (Time Frame - Day 84):
safety and tolerability will be reported separately following single-dose administration.

2. Incidence of treatment-emergent adverse events (Time Frame - Day 140):
safety and tolerability will be reported separately following multi-dose administration.

Secondary outcome:

1. Pharmacokinetic: peak plasma concentration (Cmax) (Time Frame - Day 84 and Day 140):
Will be reported separately following single-dose and multiple-dose administration.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

Studien-Arme

  • Experimental: 1.0mg/kg - Thalassaemia
  • Experimental: 3.0mg/kg - Thalassaemia
  • Experimental: 10.0mg/kg - Thalassaemia
  • Placebo Comparator: Placebo - Thalassaemia
  • Experimental: Xmg/kg - Thalassaemia
  • Experimental: 1.0mg/kg - Myelodysplastic Syndrome
  • Experimental: 3.0mg/kg - Myelodysplastic Syndrome
  • Experimental: 10.0mg/kg - Myelodysplastic Syndrome
  • Experimental: Xmg/kg - Myelodysplastic Syndrome
  • Experimental: 3.0mg/kg - Thalassaemia multi dose
  • Experimental: 10.0mg/kg - Thalassaemia multi dose
  • Experimental: Xmg/kg - Thalassaemia multi dose
  • Experimental: 3.0mg/kg - Myelodysplastic Syndrome multi dose
  • Experimental: 10.0mg/kg - Myelodysplastic Syndrome multi dose
  • Experimental: Xmg/kg - Myelodysplastic Syndrome multi dose
  • Placebo Comparator: Placebo - Thalassaemia multi dose
  • Placebo Comparator: Placebo - Myelodysplastic Syndrome
  • Placebo Comparator: Placebo - Myelodysplastic Syndrome multi dose

Geprüfte Regime

  • SLN124:
    SLN124 for subcutaneous (s.c.) injection
  • Placebo:
    Sodium chloride for s.c. injection

Quelle: ClinicalTrials.gov


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