Non-transfusion-dependent ThalassemiaPhase 1NCT04176653
Study in Beta-thalassaemia or Myelodysplastic Syndrome Patients to Investigate the Safety and Tolerability of SLN124
A Phase 1 study of Non-transfusion-dependent Thalassemia and Low Risk Myelodysplastic Syndrome, run by Silence Therapeutics plc at 5 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-transfusion-dependent Thalassemia, Low Risk Myelodysplastic Syndrome
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 20 Aug 2019to 14 Oct 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Bulgaria4 sites
MHAT Dr. Nikola Vasiliev AD
Kyustendil
UMHAT Dr. Georgi Stranski AD
Pleven
Medical Center COMAC MEDICAL
Sofia
UMHAT Sv. Ivan Rilski
Sofia
About this study
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
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.
- Being tested
- SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as PlaceboDrug
IMP will be provided as a solution to be injected by qualified clinical staff in patient's abdomen, upper arms or front of the thighs.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo |
| 0.3 mg/kg | Experimental | Not described Receives: Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo |
| 1.0 mg/kg | Experimental | Not described Receives: Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo |
| 3.0 mg/kg | Experimental | Not described Receives: Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo |
| 10.0 mg/kg | Experimental | Not described Receives: Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
# 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
Measured: Up to two months
12 lead electrocardiogram parameters included PR, QTcF and QTcB will be measured from baseline to post dose follow up
Measured: Up to two months
clinical chemistry, haematology, urinalysis, liver function tests (included ALT, AST, GGT) will be measured from baseline to post dose follow up
Measured: Up to two months
height, weight, blood pressure, heart rate, respiration rate and temperature will be measured from baseline to post dose follow up
Measured: Up to two months
Secondary outcomes (3)
Biomarkers will be measured from baseline to post dose follow up
serum hepcidin level (ng/ml), ferritin level (ug/L), Transferrin saturation (%), iron level (umol/L), haemoglobin and reticulocyte count will be analysed by central laboratory.
Measured: Up to two months
Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up
Peak Plasma Concentration (Cmax) will be analysed by central laboratory.
Measured: Up to two months
Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up
Area under the plasma concentration versus time curve (AUC) will be analysed by central laboratory.
Measured: Up to two months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2019
- Study start20 Aug 2019
- Primary completion30 Sep 2021 (estimated)
- Study completion14 Oct 2021 (estimated)
Why it stopped: Study stopped prior to subject administered first dose, due to COVID-19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-transfusion-dependent ThalassemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multiple Group Assignment
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Silence Therapeutics plc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04176653
- Sponsor's protocol ID
- SLN124-001
- Status last verified
- Apr 2020
- First submitted
- 7 Nov 2019
- Last updated
- 27 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04176653
- Acronym / sponsor ID
- SLN124-001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study stopped prior to subject administered first dose, due to COVID-19
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Silence Therapeutics plcIndustry (pharma, biotech, devices)
- Study start
- 20 Aug 2019 (actual)
- Primary completion
- 30 Sep 2021 (estimated)
- Study completion
- 14 Oct 2021 (estimated)
- First posted
- 25 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
- Model description
- Multiple Group Assignment
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo |
| 0.3 mg/kg | Experimental | Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo |
| 1.0 mg/kg | Experimental | Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo |
| 3.0 mg/kg | Experimental | Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo |
| 10.0 mg/kg | Experimental | Drug: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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%
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as PlaceboIMP will be provided as a solution to be injected by qualified clinical staff in patient's abdomen, upper arms or front of the thighs. | Drug | 0.3 mg/kg, 1.0 mg/kg, 10.0 mg/kg, 3.0 mg/kg, Placebo |
Primary outcome
# 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
Time frame: Up to two months
12 lead electrocardiogram parameters included PR, QTcF and QTcB will be measured from baseline to post dose follow up
Time frame: Up to two months
clinical chemistry, haematology, urinalysis, liver function tests (included ALT, AST, GGT) will be measured from baseline to post dose follow up
Time frame: Up to two months
height, weight, blood pressure, heart rate, respiration rate and temperature will be measured from baseline to post dose follow up
Time frame: Up to two months
3 secondary outcomes
Biomarkers will be measured from baseline to post dose follow up
Time frame: Up to two months
Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up
Time frame: Up to two months
Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up
Time frame: Up to two months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study of Non-transfusion-dependent Thalassemia and Low Risk Myelodysplastic Syndrome, run by Silence Therapeutics plc at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 27 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Bulgaria, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Up to two months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2020.