SLN124 for Polycythemia Vera

(SLN Trial)

Recruiting at 22 trial locations

Overseen By Silence Therapeutics Patient Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Silence Therapeutics plc

Must be taking: Cytoreductive therapy

Must not be taking: Investigational drugs

Disqualifiers: Thrombosis, Major bleeding, Myelofibrosis, others

Compensation: Varies

Number of Visits: Unknown

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SLN124 for individuals with Polycythemia Vera (PV), a condition characterized by the overproduction of red blood cells. The study aims to determine the safety of SLN124, how the body processes it, and its effectiveness in managing PV. Participants will receive either SLN124 or a placebo (a substance with no active treatment). Suitable candidates for this trial are adults diagnosed with PV who have a history of needing regular blood draws and do not plan to change their current treatment soon. As a Phase 1, Phase 2 trial, this research focuses on understanding how SLN124 works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

If you are not on cytoreductive therapy, you must have stopped any previous cytoreductive medications at least 24 weeks before starting the trial. If you are on cytoreductive therapy like hydroxyurea, interferon, busulfan, or ruxolitinib, you need to be on a stable dose for at least 12 weeks before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that SLN124, also known as divesiran, appears safe for use. Studies have found it to be safe and well-tolerated in people with Polycythemia Vera (PV). Early research reported no major safety issues, indicating that participants generally did not experience serious side effects. The treatment also demonstrated some positive effects in initial tests. These findings suggest that SLN124 could be a safe option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Polycythemia Vera?

Most treatments for polycythemia vera, like phlebotomy and hydroxyurea, focus on reducing blood cell counts or controlling symptoms. But SLN124 works differently, targeting the body's iron regulation to potentially reduce the production of red blood cells. This innovative approach could offer a new way to manage polycythemia vera by directly influencing the underlying mechanism of the disease. Researchers are excited about SLN124 because it introduces a novel mechanism of action, which might lead to more effective and targeted treatments with potentially fewer side effects.

What evidence suggests that SLN124 might be an effective treatment for Polycythemia Vera?

Research has shown that SLN124, also known as Divesiran, could help treat polycythemia vera (PV). It increases a protein called hepcidin, which controls iron levels in the body, by turning off a gene called TMPRSS6. This process reduces iron in the blood, aiding in PV management. Early studies suggest that SLN124 is safe and shows promising effectiveness in patients with PV. In this trial, participants will receive either SLN124 or a placebo to further evaluate its potential as a treatment for polycythemia vera. Overall, these initial results support further research into SLN124 as a potential treatment for polycythemia vera. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

Adults with Polycythemia Vera (PV) who've had a skin check in the last 6 months, meet specific PV diagnostic criteria, and have stable phlebotomy history. They must not be on or have recently used certain drugs for PV, agree to contraception, and have an acceptable level of physical functioning.

Inclusion Criteria

I have seen a skin doctor in the last 6 months.

Suitable phlebotomy history

I have been diagnosed with polycythemia vera according to the latest criteria.

Exclusion Criteria

I have had major bleeding or needed a blood transfusion due to bleeding in the last 6 months.

History of intolerance to oligonucleotides, or GalNAc, or any component of SLN124

Hematological parameters at screening as follows: platelets 1,000,000/µL; or white blood cell (WBC) count > 25,000/µL; or peripheral blasts < 1%

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Dose Escalation

Participants receive SLN124 in an open-label dose escalation to assess safety, tolerability, and pharmacokinetics

8 weeks

Randomized Double-blind Phase

Participants are randomized to receive either SLN124 or placebo in a double-blind manner to assess efficacy and pharmacodynamics

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• SLN124

Trial Overview The study is testing SLN124 against a placebo in patients with PV. It starts with an open-label phase where everyone gets SLN124 to find safe doses, followed by a randomized phase where participants are blindly given either SLN124 or a placebo to compare effects.

How Is the Trial Designed?

Group I: Phase 2 Blinded SLN124 Experimental Treatment 1 Intervention

SLN124 for subcutaneous (s.c.) injection

Group II: Phase 1 open-label SLN124 Experimental Treatment 1 Intervention

SLN124 for subcutaneous (s.c.) injection

Group III: Phase 2 Blinded Placebo Placebo Group 1 Intervention

Sodium chloride for s.c. injection

Who Is Running the Clinical Trial?

Silence Therapeutics plc

Lead Sponsor

Trials

6

Recruited

380+

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/656/530672/Initial-Results-from-a-Phase-1-2-Study-Evaluating

Initial Results from a Phase 1/2 Study Evaluating Divesiran, a ... Divesiran (SLN124), a liver-targeted GalNAc-conjugated double-stranded 19-mer siRNA increases hepatic hepcidin synthesis and plasma levels by silencing TMPRSS6.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05499013

Study to Assess 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37497888/

SLN124, a GalNAc conjugated 19-mer siRNA targeting ... SLN124, a GalNAc conjugated 19-mer siRNA targeting tmprss6, reduces plasma iron and increases hepcidin levels of healthy volunteers · Abstract.

4. onclive.com onclive.com/view/divesiran-is-tolerable-and-shows-positive-early-signals-in-polycythemia-vera

Divesiran Is Tolerable and Shows Positive Early Signals in ... Divesiran (SLN124), a novel small interfering RNA (siRNA), was safe and displayed signals of efficacy in the treatment of patients with polycythemia vera.

5. silence-therapeutics.com silence-therapeutics.com/investors/press-releases/press-releases-details/2024/Silence-Therapeutics-Announces-Positive-Results-from-Ongoing-SANRECO-Phase-1-Study-of-Divesiran-in-Polycythemia-Vera-Patients/default.aspx

Press Releases Details Silence Therapeutics Announces Positive Results from Ongoing SANRECO Phase 1 Study of Divesiran in Polycythemia Vera Patients. 06/27/2024.