Study to Assess SLN124 in Patients With Polycythemia Vera (SLN)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Polycythemia Vera
• Intervention / Treatment: Drug: SLN124; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Benowa, Australia
    • Research Site
  • Hobart, Australia
    • Research Site
  • Kurralta Park, Australia
    • Research Site
  • Melbourne, Australia
    • Research Site
  • Melbourne, Australia
    • Research Site 2
  • Nedlands, Australia
    • Linear Clinical Research
  • Richmond, Australia
    • Research Site
• Bulgaria
  • Plovdiv, Bulgaria
    • Research Site
  • Plovdiv, Bulgaria
    • Research Site 2
• Canada
  • Toronto, Canada
    • Research Site
• Germany
  • Freiburg im Breisgau, Germany
    • Research Site
  • Hanover, Germany
    • Research Site
• Italy
  • Alessandria, Italy
    • Research Site
  • Meldola, Italy
    • Research Site
• Malaysia
  • Johor Bahru, Malaysia
    • Research Site
  • Kuala Terengganu, Malaysia
    • Research Site
  • Kuantan, Malaysia
    • Research Site
  • Kuching, Malaysia
    • Research Site
• Poland
  • Gdansk, Poland
    • Research Site
  • Katowice, Poland
    • Research Site
  • Lublin, Poland
    • Research Site
• Spain
  • Barcelona, Spain
    • Research Site
  • Madrid, Spain
    • Research Site
• United States
  • Louisiana
    • Hammond, Louisiana, United States, 70403
      • Research Site
  • New York
    • Buffalo, New York, United States, 14203
      • Research Site
    • New York, New York, United States, 10029
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Research Site
  • Texas
    • Huntsville, Texas, United States, 77340
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Phase 1 and Phase 2

Inclusion Criteria:

• 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.

Exclusion Criteria:

Phase 1 and Phase 2

• Drug intolerance:

  1. History of intolerance to oligonucleotides, or GalNAc, or any component of SLN124.
  2. 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.
• 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:

  1. Biochemical evidence of significant liver disease during screening
  2. 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%.

  b. Phase 2: Hematological parameters at screening as follows: platelets > 1,000,000/µL; or WBC count > 30,000/µL; or peripheral blasts > 1%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 open-label SLN124; SLN124 for subcutaneous (s.c.) injection	Drug: SLN124; SLN124 is a double-stranded small interfering ribonucleic acid (siRNA) targeting transmembrane protease, serine 6 (TMPRSS6) messenger ribonucleic acid (mRNA).
Experimental: Phase 2 Blinded SLN124; SLN124 for subcutaneous (s.c.) injection	Drug: SLN124; SLN124 is a double-stranded small interfering ribonucleic acid (siRNA) targeting transmembrane protease, serine 6 (TMPRSS6) messenger ribonucleic acid (mRNA).
Placebo Comparator: Phase 2 Blinded Placebo; Sodium chloride for s.c. injection	Drug: Placebo; sodium chloride, solution for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 239
Phase 1: Assessment of the number of phlebotomies at intervals		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)		18 to 36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Pharmacokinetic: area under the plasma concentration (AUC)		Day 127
Phase 1: Pharmacokinetic: peak plasma concentration (Cmax)		Day 127
Phase 1: Pharmacodynamic: change in haematocrit		Day 1 to Day 239
Phase 1: Pharmacodynamic: Change in Transferrin saturation (TSAT)		Day 1 to Day 239
Phase 1: Pharmacodynamic: Change in Hepcidin		Day 1 to Day 239
Phase 2: Comparison of the effect of SLN124 vs placebo	Number of phlebotomies	Over 36 weeks
Phase 2: Comparison of the effect of SLN124 vs placebo	Proportion of patients who achieve a response	Over 36 weeks
Phase 2: Comparison of the effect of SLN124 vs placebo	Safety and tolerability	Over 36 weeks
Phase 2: Comparison of the effect of SLN124 vs placebo	Hematology parameters and biomarkers of iron metabolism	Over 36 weeks
Phase 2: In the double-blind extension period and in the OLE period:	Assess long-term safety and tolerability of SLN124	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	Week 37 to Week 181
Phase 2: Assessment of SLN124 Cmax at Day 1 and Day 169 of the trial.		Day 1 and Day 169
Phase 2: Assessment of SLN124 PD	Hepcidin	Changes from Week 1 to Week 181
Phase 2: Assessment of QoL	MPN-SAF-TSS	Changes from Week 1 to Week 181
Phase 2: Assessment of QoL	PGI-C	Changes from Week 1 to Week 181
Phase 2: Pharmacodynamic: Change in haematocrit		Changes from Week 1 to Week 181
Phase 2: Pharmacodynamic: Change in Hepcidin		Changes from Week 1 to Week 181

Collaborators and Investigators

• Sponsor: Silence Therapeutics plc

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: July 29, 2022
• First Submitted That Met QC Criteria: August 10, 2022
• First Posted (Actual): August 12, 2022

Study Record Updates

• Last Update Posted (Estimated): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: PV
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Hemic and Lymphatic Diseases; Polycythemia Vera
• Other Study ID Numbers: SLN124-004; SANRECO (Other Identifier: Silence Therapeutics)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No