Study to Assess SLN124 in Patients With Polycythemia Vera

Polycythemia Vera Clinical Trial

— SLN  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05499013
• Other study ID #: SLN124-004
• Secondary ID: SANRECO
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 26, 2023
• Est. completion date: June 2025

Study information

• Verified date: April 2024
• Source: Silence Therapeutics plc
• Contact: Silence Therapeutics Patient Information
• Phone: +44 (0) 20 3457 6900
• Email: patient-info[@]silence-therapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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%.

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera

Intervention

Drug:
• SLN124
SLN124 is a double-stranded small interfering ribonucleic acid (siRNA) targeting transmembrane protease, serine 6 (TMPRSS6) messenger ribonucleic acid (mRNA).
• Placebo
sodium chloride, solution for injection

Locations

Country	Name	City	State
Australia	Pindara Private Hospital	Benowa	Queensland
Australia	Ashford Cancer Centre Research	Kurralta Park	South Australia
Australia	Alfred Health	Melbourne	Victoria
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Linear Clinical Research	Nedlands	Western Australia
Australia	Epworth HealthCare	Richmond	Victoria
Bulgaria	MHAT Dr Nikola Vasiliev AD	Kyustendil
Bulgaria	Medical Centre Leo Clinic EOOD	Plovdiv
Malaysia	Hospital Ampang	Ampang	Selangor
Malaysia	Hospital Sultanah Aminah	Johor Bahru	Johor
Malaysia	Hospital Sultanah Nur Zahirah	Kuala Terengganu	Terengganu
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan	Pahang
Malaysia	Hospital Umum Sarawak	Kuching	Sarawak
Poland	Uniwersyteckie Centrum Klinlczne	Gdansk
Poland	PRATIA Hematologia Sp. z o. o.	Katowice
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie	Lublin
Poland	Centrum Medyczne Pratia Poznan Sp. z o. o.	Skorzewo
Poland	Specjalistyczny Szpital Im Dra. A.	Walbrzych
United States	University of Michigan	Ann Arbor	Michigan
United States	Duke Cancer Institute	Durham	North Carolina
United States	North Houston Cancer Clinics	Huntsville	Texas
United States	Mount Sinai Hospital	New York	New York
United States	Renovatio Clinical	The Woodlands	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Silence Therapeutics plc

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Malaysia,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Assessment of the number of phlebotomies at intervals		6 months prior to dosing to Day 239
Secondary	Pharmacokinetic: area under the plasma concentration (AUC)		Day 127
Secondary	Pharmacokinetic: peak plasma concentration (Cmax)		Day 127
Secondary	Pharmacodynamic: change in haematocrit		Day 1 to Day 239
Secondary	Pharmacodynamic: Change in Transferrin saturation (TSAT)		Day 1 to Day 239
Secondary	Pharmacodynamic: Change in Hepcidin		Day 1 to Day 239