Polycythemia VeraPhase 1/2SLNNCT05499013
Study to Assess SLN124 in Patients With Polycythemia Vera
A Phase 1/2 study testing SLN124 in people with Polycythemia Vera, run by Silence Therapeutics plc at 28 sites in 9 countries.
Trial summary
This is a Phase 1/2, multicenter study with an open-label dose escalation followed by a randomized placebo controlled and double-blind phase of SLN124 in adult patients with Polycythemia Vera (PV) to assess the safety, tolerability, efficacy, pharmacokinetic (PK), and Pharmacodynamic (PD) response of SLN124. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polycythemia Vera
- What is being tested?
- SLN124
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 28 sitesin 9 countries
- Study dates
- 26 Jan 2023to Mar 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- Male and female patients aged 18 years or older.
- A confirmed diagnosis of PV according to the revised 2016 World Health Organization criteria:
- Suitable phlebotomy history
- Must agree to adhere to appropriate contraception requirements
- Patients who are not receiving cytoreductive therapy must have been discontinued from any prior cytoreductive therapy for at least 24 weeks before dosing and have recovered from any adverse events due to cytoreductive therapy.
- Patients receiving cytoreductive therapy with hydroxyurea, interferon, busulfan or ruxolitinib must have received a stable dose of cytoreductive therapy for at least 12 weeks before dosing and with no planned change in dose.
- Patients must have had a dermatological examination within 28 weeks prior to dosing.
- Must have an Eastern Cooperative Oncology Group score of 0, 1, or 2.
Who cannot join
- Phase 1 and Phase 2
- Drug intolerance:
- History of intolerance to oligonucleotides, or GalNAc, or any component of SLN124.
- History of intolerance to s.c. injections.
- Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 12 weeks of screening.
- History of major bleeding events and/or a requirement for blood transfusion therapy owing to bleeding in the last 6 months prior to screening.
Show all 14Show fewer
- Meets the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment
- Any investigational drug less than 6 weeks prior to the first dose of study drug or not recovered from effects of prior administration of any investigational agent.
- Any investigational or marketed product using GalNAc targeting less than 48 weeks prior to administration of any investigational agent (excludes patients with PV who participated in Phase 1 of this study).
- Clinically significant co-morbidities
- Biochemical and hematological parameters:
- Biochemical evidence of significant liver disease during screening
- Phase 1: Hematological parameters at screening as follows: platelets > 1,000,000/µL; or white blood cell (WBC) count > 25,000/µL; or peripheral blasts > 1%.
- Phase 2: Hematological parameters at screening as follows: platelets > 1,000,000/µL; or WBC count > 30,000/µL; or peripheral blasts > 1%.
Trial locations and contacts
28 sites in 9 countries.
28 sites in 9 countries
Australia7 sites
Research Site
Benowa
Research Site
Hobart
Research Site
Kurralta Park
Research Site 2
Melbourne
Research Site
Melbourne
Linear Clinical Research
Nedlands
Research Site
Richmond
United States5 sites
Research Site
Buffalo, New York, 14203
Research Site
Columbus, Ohio, 43210
Research Site
Hammond, Louisiana, 70403
Research Site
Huntsville, Texas, 77340
Research Site
New York, New York, 10029
Malaysia4 sites
Research Site
Johor Bahru
Research Site
Kuala Terengganu
Research Site
Kuantan
Research Site
Kuching
About this study
Official title: Phase 1/2 Study With an Open-label Dose Escalation Phase Followed by a Randomized, Double-blind Phase of SLN124 in Patients With Polycythemia Vera
This is a Phase 1/2, multicenter study with an open-label dose escalation followed by a randomized placebo controlled and double-blind phase of SLN124 in adult patients with Polycythemia Vera (PV) to assess the safety, tolerability, efficacy, pharmacokinetic (PK), and Pharmacodynamic (PD) response of SLN124.
- Conditions
- Polycythemia Vera
- Being tested
- SLN124, Placebo
- Keywords
- PV
- Medical subject headings
- Polycythemia Vera
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SLN124Drug
SLN124 is a double-stranded small interfering ribonucleic acid (siRNA) targeting transmembrane protease, serine 6 (TMPRSS6) messenger ribonucleic acid (mRNA).
PlaceboDrug
sodium chloride, solution for injection
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 open-label SLN124 | Experimental | SLN124 for subcutaneous (s.c.) injection Receives: Drug: SLN124 |
| Phase 2 Blinded SLN124 | Experimental | SLN124 for subcutaneous (s.c.) injection Receives: Drug: SLN124 |
| Phase 2 Blinded Placebo | Placebo comparator | Sodium chloride for s.c. injection Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Incidence of treatment-emergent adverse events (AEs)
Safety and tolerability will be reported separately following open-label dose escalation phase and double-blind phase
Measured: Day 239
Phase 1: Assessment of the number of phlebotomies at intervals
Measured: 6 months prior to dosing to Day 239
Phase 2: Proportion of patients who achieve response between week 18 and week 36 (placebo controlled double blind phase)
Measured: 18 to 36 weeks
Secondary outcomes (17)
Phase 1: Pharmacokinetic: area under the plasma concentration (AUC)
Measured: Day 127
Phase 1: Pharmacokinetic: peak plasma concentration (Cmax)
Measured: Day 127
Phase 1: Pharmacodynamic: change in haematocrit
Measured: Day 1 to Day 239
Phase 1: Pharmacodynamic: Change in Transferrin saturation (TSAT)
Measured: Day 1 to Day 239
Phase 1: Pharmacodynamic: Change in Hepcidin
Measured: Day 1 to Day 239
Phase 2: Comparison of the effect of SLN124 vs placebo
Number of phlebotomies
Measured: Over 36 weeks
Phase 2: Comparison of the effect of SLN124 vs placebo
Proportion of patients who achieve a response
Measured: Over 36 weeks
Phase 2: Comparison of the effect of SLN124 vs placebo
Safety and tolerability
Measured: Over 36 weeks
Phase 2: Comparison of the effect of SLN124 vs placebo
Hematology parameters and biomarkers of iron metabolism
Measured: Over 36 weeks
Phase 2: In the double-blind extension period and in the OLE period:
Assess long-term safety and tolerability of SLN124
Measured: Week 37 to Week 181
Phase 2: In the double-blind extension period and in the OLE period:
Assess long-term effects of SLN124 on QoL assessments
Measured: Week 37 to Week 181
Phase 2: Assessment of SLN124 Cmax at Day 1 and Day 169 of the trial.
Measured: Day 1 and Day 169
Phase 2: Assessment of SLN124 PD
Hepcidin
Measured: Changes from Week 1 to Week 181
Phase 2: Assessment of QoL
MPN-SAF-TSS
Measured: Changes from Week 1 to Week 181
Phase 2: Assessment of QoL
PGI-C
Measured: Changes from Week 1 to Week 181
Phase 2: Pharmacodynamic: Change in haematocrit
Measured: Changes from Week 1 to Week 181
Phase 2: Pharmacodynamic: Change in Hepcidin
Measured: Changes from Week 1 to Week 181
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2022
- Study start26 Jan 2023
- Primary completionSep 2026 (estimated)
- Study completionMar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycythemia VeraStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase 1 is an open-label, dose-finding study. Phase 2 is a randomized, double-blind, placebo-controlled study.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 69 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
- NCT05499013
- Sponsor's protocol ID
- SLN124-004
- Other IDs
- SANRECO
- Acronym
- SLN
- Status last verified
- Dec 2025
- First submitted
- 29 Jul 2022
- Last updated
- 19 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Study With an Open-label Dose Escalation Phase Followed by a Randomized, Double-blind Phase of SLN124 in Patients With Polycythemia Vera
- ClinicalTrials.gov ID
- NCT05499013
- Acronym / sponsor ID
- SLN / SLN124-004
- Conditions
- Polycythemia Vera
- Keywords
- PV
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Silence Therapeutics plcIndustry (pharma, biotech, devices)
- Study start
- 26 Jan 2023 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Mar 2030 (estimated)
- First posted
- 12 Aug 2022 (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.
This is a Phase 1/2, multicenter study with an open-label dose escalation followed by a randomized placebo controlled and double-blind phase of SLN124 in adult patients with Polycythemia Vera (PV) to assess the safety, tolerability, efficacy, pharmacokinetic (PK), and Pharmacodynamic (PD) response of SLN124.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Phase 1 is an open-label, dose-finding study. Phase 2 is a randomized, double-blind, placebo-controlled study.
| Arm | Type | Receives |
|---|---|---|
| Phase 1 open-label SLN124 | Experimental | Drug: SLN124SLN124 for subcutaneous (s.c.) injection |
| Phase 2 Blinded SLN124 | Experimental | Drug: SLN124SLN124 for subcutaneous (s.c.) injection |
| Phase 2 Blinded Placebo | Placebo comparator | Drug: PlaceboSodium chloride for s.c. injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female patients aged 18 years or older.
- A confirmed diagnosis of PV according to the revised 2016 World Health Organization criteria:
- Suitable phlebotomy history
- Must agree to adhere to appropriate contraception requirements
- Patients who are not receiving cytoreductive therapy must have been discontinued from any prior cytoreductive therapy for at least 24 weeks before dosing and have recovered from any adverse events due to cytoreductive therapy.
Key exclusion criteria (14 listed)
- Phase 1 and Phase 2
- Drug intolerance:
- Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 12 weeks of screening.
- History of major bleeding events and/or a requirement for blood transfusion therapy owing to bleeding in the last 6 months prior to screening.
- Meets the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment
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 |
|---|---|---|
| SLN124SLN124 is a double-stranded small interfering ribonucleic acid (siRNA) targeting transmembrane protease, serine 6 (TMPRSS6) messenger ribonucleic acid (mRNA). | Drug | Phase 1 open-label SLN124, Phase 2 Blinded SLN124 |
| Placebosodium chloride, solution for injection | Drug | Phase 2 Blinded Placebo |
Primary outcome
Phase 1: Incidence of treatment-emergent adverse events (AEs)
Time frame: Day 239
Safety and tolerability will be reported separately following open-label dose escalation phase and double-blind phase
Phase 1: Assessment of the number of phlebotomies at intervals
Time frame: 6 months prior to dosing to Day 239
Phase 2: Proportion of patients who achieve response between week 18 and week 36 (placebo controlled double blind phase)
Time frame: 18 to 36 weeks
17 secondary outcomes
Phase 1: Pharmacokinetic: area under the plasma concentration (AUC)
Time frame: Day 127
Phase 1: Pharmacokinetic: peak plasma concentration (Cmax)
Time frame: Day 127
Phase 1: Pharmacodynamic: change in haematocrit
Time frame: Day 1 to Day 239
Phase 1: Pharmacodynamic: Change in Transferrin saturation (TSAT)
Time frame: Day 1 to Day 239
Phase 1: Pharmacodynamic: Change in Hepcidin
Time frame: Day 1 to Day 239
Phase 2: Comparison of the effect of SLN124 vs placebo
Time frame: Over 36 weeks
Phase 2: Comparison of the effect of SLN124 vs placebo
Time frame: Over 36 weeks
Phase 2: Comparison of the effect of SLN124 vs placebo
Time frame: Over 36 weeks
Phase 2: Comparison of the effect of SLN124 vs placebo
Time frame: Over 36 weeks
Phase 2: In the double-blind extension period and in the OLE period:
Time frame: Week 37 to Week 181
Phase 2: In the double-blind extension period and in the OLE period:
Time frame: Week 37 to Week 181
Phase 2: Assessment of SLN124 Cmax at Day 1 and Day 169 of the trial.
Time frame: Day 1 and Day 169
Phase 2: Assessment of SLN124 PD
Time frame: Changes from Week 1 to Week 181
Phase 2: Assessment of QoL
Time frame: Changes from Week 1 to Week 181
Phase 2: Assessment of QoL
Time frame: Changes from Week 1 to Week 181
Phase 2: Pharmacodynamic: Change in haematocrit
Time frame: Changes from Week 1 to Week 181
Phase 2: Pharmacodynamic: Change in Hepcidin
Time frame: Changes from Week 1 to Week 181
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2025.
Related trials for Polycythemia Vera
RecruitingPhase 3
A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (PPV-MF)
RecruitingPhase 2/3
A Clinical Trial of Bomedemstat in Participants With Polycythemia Vera (MK-3543-025).
Polycythemia Vera
RecruitingPhase 2
Study of Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Myelofibrosis
Primary Myelofibrosis, Myelofibrosis; Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
RecruitingPhase 2
A Study of Ropeg-Interferon in People With Polycythemia Vera
Polycythemia Vera (PV), JAK2 Mutation
Active, not recruitingPhase 2
A Phase 2, Open-Label Study of DISC-3405 in Participants With Polycythemia Vera (PV)
Polycythemia Vera (PV)
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.
28 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SLN124 in people with Polycythemia Vera, run by Silence Therapeutics plc at 28 sites in 9 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 8 inclusion and 14 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: under way, not looking for participants, as of the sponsor's last update on 19 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in Australia, United States, Malaysia, Poland, Bulgaria and 4 more countries. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Phase 1: Incidence of treatment-emergent adverse events (AEs) (time frame: Day 239). The study lists 3 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 19 Dec 2025.