Clinical trial NCT05499013: Study to Assess SLN124 in Patients With Polycythemia Vera
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Polycythemia Vera
Keywords: PV
Lead sponsor: Silence Therapeutics plc
Sponsor class: INDUSTRY
First posted: 2022-08-12
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1 is an open-label, dose-finding study. Phase 2 is a randomized, double-blind, placebo-controlled study.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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%.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (AEs)
timeFrame: Day 239
measure: Assessment of the number of phlebotomies at intervals
timeFrame: 6 months prior to dosing to Day 239
Secondary outcomes:
measure: Pharmacokinetic: area under the plasma concentration (AUC)
timeFrame: Day 127
measure: Pharmacokinetic: peak plasma concentration (Cmax)
timeFrame: Day 127
measure: Pharmacodynamic: change in haematocrit
timeFrame: Day 1 to Day 239
measure: Pharmacodynamic: Change in Transferrin saturation (TSAT)
timeFrame: Day 1 to Day 239
measure: Pharmacodynamic: Change in Hepcidin
timeFrame: Day 1 to Day 239
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Huntsville
country: United States
facility: North Houston Cancer Clinics
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre Research
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Richmond
country: Australia
facility: Epworth HealthCare
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Kyustendil
country: Bulgaria
facility: MHAT Dr Nikola Vasiliev AD
city: Plovdiv
country: Bulgaria
facility: Medical Centre Leo Clinic EOOD
city: Johor Bahru
country: Malaysia
facility: Hospital Sultanah Aminah
state: Johor
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
state: Pahang
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
state: Sarawak
city: Ampang
country: Malaysia
facility: Hospital Ampang
state: Selangor
city: Kuala Terengganu
country: Malaysia
facility: Hospital Sultanah Nur Zahirah
state: Terengganu
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Klinlczne
city: Katowice
country: Poland
facility: PRATIA Hematologia Sp. z o. o.
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie
city: Skorzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan Sp. z o. o.
city: Wałbrzych
country: Poland
facility: Specjalistyczny Szpital Im Dra. A.
Study officials:
References: