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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Phlebotomy Dependent Polycythemia Vera
• Intervention / Treatment: Drug: sapablursen

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 9 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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Albury, Australia, 2640
    • Border Medical Oncology Research Unit
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle Hospital
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
• Poland
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie, Klinika Hematoonkologii i Transplantacji Szpiku
  • Słupsk, Poland, 76-200
    • Wojewódzki Szpital Specjalistyczny Sp. z o.o.
  • Torun, Poland, 87-100
    • MICS Centrum Medyczne Torun
• United Kingdom
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals NHS Foundation Trust
  • England
    • Oxford, England, United Kingdom, OX37LE
      • Oxford University Hospitals NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • O'Neal Comprehensive Cancer Center University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Meet modified World Health Organization (WHO) 2016 diagnostic criteria for polycythemia vera (PV) at the time of clinical diagnosis
2. Participant must be phlebotomy dependent.
3. 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

1. Meets criteria for post-polycythemia vera myelofibrosis (PPV-MF) as defined by the International Working Group- Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
2. Moderate to severe splenic pain or spleen-related organ obstruction
3. Active or chronic bleeding within 1 month of Screening, significant concurrent/recent coagulopathy, history of immune thrombocytopenic purpura (ITP)
4. Known primary or secondary immunodeficiency
5. Active infection with human immunodeficiency virus (HIV), hepatitis C, or hepatitis B.
6. Active infection requiring systemic antiviral or antimicrobial therapy or active novel coronavirus disease (Covid-19) infection
7. 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
8. Surgery requiring general anesthesia within 1 month prior to Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sapablursen Dose Level 1; Sapablursen will be administered by SC injection every 4 weeks.	Drug: sapablursen; Sapablursen will be administered by SC injection.; Other Names: ISIS 702843; IONIS-TMPRSS6-LRx
Experimental: Sapablursen Dose Level 2; Sapablursen will be administered by SC injection every 4 weeks	Drug: sapablursen; Sapablursen will be administered by SC injection.; Other Names: ISIS 702843; IONIS-TMPRSS6-LRx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2021
• Primary Completion (Actual): June 26, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: November 20, 2021
• First Submitted That Met QC Criteria: November 20, 2021
• First Posted (Actual): December 3, 2021

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Polycythemia Vera
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Hemic and Lymphatic Diseases; Polycythemia Vera
• Other Study ID Numbers: ISIS 702843-CS4; 2021-003704-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No