Study to Assess SLN124 in Patients With Polycythemia Vera

Phase 1

Recruiting

• Conditions: Polycythemia Vera
• Interventions: Drug: SLN124; Drug: Placebo

• Registration Number: NCT05499013
• Lead Sponsor: Silence Therapeutics plc

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-07-29
• Study First Submitted QC: 2022-08-10
• Study First Posted: 2022-08-12
• Study Start: 2023-01-26
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-19
• Last Update Posted: 2024-04-22
• Primary Completion: 2024-12
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 65

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 6 months prior to screening.
• Must have an Eastern Cooperative Oncology Group score of 0, 1, or 2.

Exclusion Criteria

• 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.

• Clinically significant co-morbidities

• Biochemical and hematological parameters:

  1. Biochemical evidence of significant liver disease during screening
  2. Hematological parameters at screening as follows: platelets 1,000,000/µL; or white blood cell (WBC) count > 25,000/µL; or peripheral blasts < 1%.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2 Blinded SLN124	SLN124	SLN124 for subcutaneous (s.c.) injection
Phase 2 Blinded Placebo	Placebo	Sodium chloride for s.c. injection
Phase 1 open-label SLN124	SLN124	SLN124 for subcutaneous (s.c.) injection

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events (AEs)	Day 239	Safety and tolerability will be reported separately following open-label dose escalation phase and double-blind phase
Assessment of the number of phlebotomies at intervals	6 months prior to dosing to Day 239

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic: area under the plasma concentration (AUC)	Day 127
Pharmacodynamic: change in haematocrit	Day 1 to Day 239
Pharmacodynamic: Change in Transferrin saturation (TSAT)	Day 1 to Day 239
Pharmacokinetic: peak plasma concentration (Cmax)	Day 127
Pharmacodynamic: Change in Hepcidin	Day 1 to Day 239

Trial Locations

Locations (23)

PRATIA Hematologia Sp. z o. o.; 🇵🇱 Katowice, Poland

Hospital Tengku Ampuan Afzan; 🇲🇾 Kuantan, Pahang, Malaysia

Linear Clinical Research; 🇦🇺 Nedlands, Western Australia, Australia

Pindara Private Hospital; 🇦🇺 Benowa, Queensland, Australia

Hospital Umum Sarawak; 🇲🇾 Kuching, Sarawak, Malaysia

Renovatio Clinical; 🇺🇸 The Woodlands, Texas, United States

Ashford Cancer Centre Research; 🇦🇺 Kurralta Park, South Australia, Australia

Alfred Health; 🇦🇺 Melbourne, Victoria, Australia

Medical Centre Leo Clinic EOOD; 🇧🇬 Plovdiv, Bulgaria

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

Hospital Sultanah Nur Zahirah; 🇲🇾 Kuala Terengganu, Terengganu, Malaysia

Hospital Sultanah Aminah; 🇲🇾 Johor Bahru, Johor, Malaysia

Centrum Medyczne Pratia Poznan Sp. z o. o.; 🇵🇱 Skorzewo, Poland

MHAT Dr Nikola Vasiliev AD; 🇧🇬 Kyustendil, Bulgaria

Epworth HealthCare; 🇦🇺 Richmond, Victoria, Australia

Mount Sinai Hospital; 🇺🇸 New York, New York, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Specjalistyczny Szpital Im Dra. A.; 🇵🇱 Wałbrzych, Poland

Uniwersyteckie Centrum Klinlczne; 🇵🇱 Gdańsk, Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie; 🇵🇱 Lublin, Poland

Duke Cancer Institute; 🇺🇸 Durham, North Carolina, United States

North Houston Cancer Clinics; 🇺🇸 Huntsville, Texas, United States

Hospital Ampang; 🇲🇾 Ampang, Selangor, Malaysia