Clinical trial NCT04176653: Study in Beta-thalassaemia or Myelodysplastic Syndrome Patients to Investigate the Safety and Tolerability of SLN124
Official title: Phase 1b Single Ascending and Multiple Dose First-in-man Study in Adult Patients With Non-transfusion-dependent Beta-thalassaemia or Low Risk Myelodysplastic Syndrome to Investigate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Response of SLN124
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Non-transfusion-dependent Thalassemia
Low Risk Myelodysplastic Syndrome
Lead sponsor: Silence Therapeutics plc
Sponsor class: INDUSTRY
First posted: 2019-11-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multiple Group Assignment
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to determine the safety and tolerability of SLN124 for the treatment of non-transfusion-dependent (NTD) β-thalassaemia and low risk myelodysplastic syndrome.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18yrs; BMI 18-35 kg/m2
* β-thalassaemia intermedia or compound heterozygous HbE/β-thalassaemia
* Non-transfusion dependent: ≤ 5 units red cells in last 6 months and transfusion-free for ≥8 weeks
* Hb between 5 \& 11 g/dL
* Ferritin \> 250 µg/L and /or liver iron ≥ 3mg Fe/g dry weight and TSAT \>40%

Exclusion Criteria:

* Haemoglobin S/β-thalassaemia, homozygous β-0 thalassaemia or α thalassaemia
* ALT/AST \> 1.5 x upper limit normal or cirrhosis
* eGFR \< 60 mL/min/1.73m2
* Platelets \<100 or \> 1000 x 109/L
* Untreated B12/folate deficiency
* Iron chelation therapy unless stable for ≥8 weeks
* Daily NSAID, therapeutic dose anticoagulant, ESA ≤12 weeks or stable dosing of hydroxyurea ≤ 6 months
* Significant cardiac disease (MI in 6 months, NYHA class III-IV heart failure, long QT)
* HIV or active hepatitis B/C or malignancy within 5 year

Primary outcomes:
measure: # of participants with all AEs as assessed by CTCAE V4.0 included injection site reaction, will be measured from baseline to post dose follow up
timeFrame: Up to two months
measure: 12 lead electrocardiogram parameters included PR, QTcF and QTcB will be measured from baseline to post dose follow up
timeFrame: Up to two months
measure: clinical chemistry, haematology, urinalysis, liver function tests (included ALT, AST, GGT) will be measured from baseline to post dose follow up
timeFrame: Up to two months
measure: height, weight, blood pressure, heart rate, respiration rate and temperature will be measured from baseline to post dose follow up
timeFrame: Up to two months
Secondary outcomes:
measure: Biomarkers will be measured from baseline to post dose follow up
timeFrame: Up to two months
measure: Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up
timeFrame: Up to two months
measure: Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up
timeFrame: Up to two months
Other outcomes:
Locations:
city: Kyustendil
country: Bulgaria
facility: MHAT Dr. Nikola Vasiliev AD
city: Pleven
country: Bulgaria
facility: UMHAT Dr. Georgi Stranski AD
city: Sofia
country: Bulgaria
facility: Medical Center COMAC MEDICAL
city: Sofia
country: Bulgaria
facility: UMHAT Sv. Ivan Rilski
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
References: