A Study to Evaluate Sapablursen (Formerly ISIS 702843, IONIS-TMPRSS6-LRx) in Patients With Polycythemia Vera

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to evaluate the efficacy of sapablursen in reducing the frequency of phlebotomy and in improving quality of life assessments in participants with polycythemia vera.

Detailed Description
-----------------
This is a Phase 2a, multi-center, randomized, open-label study of sapablursen in up to 40 participants with PD-PV. The study consists of 4 periods: 1) Screening Period: up to 7 weeks; 2) Treatment Period: 37 weeks 3) Treatment Extension Period: 36 weeks; 4) Post-treatment Period: 13 weeks. In the Treatment Period, study drug is given by subcutaneous (under the skin) injection(s). There will be a total of 10 doses given over about 8 months. In the Treatment Extension Period, there will be a total of 9 doses given over about 8 months. Participants will be assigned to receive one of 2 Dosing Levels - a higher or a lower level, with an equal chance of being assigned to either Dosing Level. All participants will receive study drug; there is no placebo. This study was extended to allow participants to receive sapablursen for an additional 36 weeks following the initial 37-week treatment period.

Official Title
-----------------
A Phase 2a, Randomized, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 702843 Administered to Patients With Phlebotomy Dependent Polycythemia Vera (PD-PV)

Conditions
-----------------
Phlebotomy Dependent Polycythemia Vera

Intervention / Treatment
-----------------
* Drug: sapablursen


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Meet modified World Health Organization (WHO) 2016 diagnostic criteria for polycythemia vera (PV) at the time of clinical diagnosis Participant must be phlebotomy dependent. Participants do not need to be on cytoreductive therapy and do not need to have been previously treated with cytoreductive therapy. If the patient was previously on cytoreductive therapy it must have been discontinued at least 3 months prior to Screening, with all associated AEs resolved. If the patient is currently on cytoreductive therapy they must be on a stable dose of hydroxyurea, recombinant or PEGylated interferon, or ruxolitinib for at least 3 months prior to Screening. Exclusion Criteria Meets criteria for post-polycythemia vera myelofibrosis (PPV-MF) as defined by the International Working Group- Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Moderate to severe splenic pain or spleen-related organ obstruction Active or chronic bleeding within 1 month of Screening, significant concurrent/recent coagulopathy, history of immune thrombocytopenic purpura (ITP) Known primary or secondary immunodeficiency Active infection with human immunodeficiency virus (HIV), hepatitis C, or hepatitis B. Active infection requiring systemic antiviral or antimicrobial therapy or active novel coronavirus disease (Covid-19) infection Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or non-metastatic prostate cancer that has been successfully treated Surgery requiring general anesthesia within 1 month prior to Screening

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sapablursen Dose Level 1<br>Sapablursen will be administered by SC injection every 4 weeks. | Drug: sapablursen<br>* Sapablursen will be administered by SC injection.<br>* Other names: IONIS-TMPRSS6-LRx;|
| Experimental: Sapablursen Dose Level 2<br>Sapablursen will be administered by SC injection every 4 weeks | Drug: sapablursen<br>* Sapablursen will be administered by SC injection.<br>* Other names: IONIS-TMPRSS6-LRx;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the frequency of phlebotomy comparing Baseline with the last 20 weeks of the 37 week Treatment Period |  | Week 17 to Week 37 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving a reduction in the frequency of phlebotomy by ≥ 30%, ≥ 50%, ≥ 75% and ≥ 90% comparing Baseline with the last 20 weeks of the 37-week Treatment Period |  | Week 17 to Week 37 | 
| Change in the Myeloproliferative Neoplasm Symptom Assessment Form-Total Symptom Score (MPN-SAF-TSS) From Baseline to Week 37 |  | Baseline up to Week 37 | 

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