Study to Assess SLN124 in Patients With Polycythemia Vera

Study Overview
=================
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.

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

Conditions
-----------------
Polycythemia Vera

Intervention / Treatment
-----------------
* Drug: SLN124
* Drug: Placebo


Participation Criteria
=================
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: History of intolerance to oligonucleotides, or GalNAc, or any component of SLN124. 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: Biochemical evidence of significant liver disease during screening Hematological parameters at screening as follows: platelets 1,000,000/µL; or white blood cell (WBC) count > 25,000/µL; or peripheral blasts < 1%.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 1 is an open-label, dose-finding study. Phase 2 is a randomized, double-blind, placebo-controlled study.
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Assessment of the number of phlebotomies at intervals |  | 6 months prior to dosing to Day 239 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic: area under the plasma concentration (AUC) |  | Day 127 | 
| Pharmacokinetic: peak plasma concentration (Cmax) |  | Day 127 | 
| Pharmacodynamic: change in haematocrit |  | Day 1 to Day 239 | 
| Pharmacodynamic: Change in Transferrin saturation (TSAT) |  | Day 1 to Day 239 | 
| Pharmacodynamic: Change in Hepcidin |  | Day 1 to Day 239 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PV