Phlebotomy Dependent Polycythemia VeraPhase 2NCT05143957
A Study to Evaluate Sapablursen (Formerly ISIS 702843, IONIS-TMPRSS6-LRx) in Patients With Polycythemia Vera
A Phase 2 study testing sapablursen in people with Phlebotomy Dependent Polycythemia Vera, run by Ionis Pharmaceuticals, Inc. at 13 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Phlebotomy Dependent Polycythemia Vera
- What is being tested?
- sapablursen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 13 sitesin 5 countries
- Study dates
- 30 Dec 2021to 2 Jun 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
13 sites in 5 countries.
13 sites in 5 countries
United States5 sites
O'Neal Comprehensive Cancer Center University of Alabama at Birmingham
Birmingham, Alabama, 35249
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
John Theurer Cancer Center
Hackensack, New Jersey, 07601
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic Hospital
Phoenix, Arizona, 85054
Poland3 sites
Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie, Klinika Hematoonkologii i Transplantacji Szpiku
Lublin, 20-081
Wojewódzki Szpital Specjalistyczny Sp. z o.o.
Słupsk, 76-200
MICS Centrum Medyczne Toruń
Torun, 87-100
Australia2 sites
Border Medical Oncology Research Unit
Albury, 2640
Calvary Mater Newcastle Hospital
Waratah, New South Wales, 2298
United Kingdom2 sites
University College London Hospitals NHS Foundation Trust
London, NW1 2PG
Oxford University Hospitals NHS Foundation Trust
Oxford, England, OX37LE
About this study
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)
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.
Read the 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.
- Conditions
- Phlebotomy Dependent Polycythemia Vera
- Being tested
- sapablursen
- Keywords
- Polycythemia Vera
- Medical subject headings
- Polycythemia Vera
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sapablursenDrug
Also called ISIS 702843, IONIS-TMPRSS6-LRx
Sapablursen will be administered by SC injection.
| Study group | Role | What they receive |
|---|---|---|
| Sapablursen Dose Level 1 | Experimental | Sapablursen will be administered by SC injection every 4 weeks. Receives: Drug: sapablursen |
| Sapablursen Dose Level 2 | Experimental | Sapablursen will be administered by SC injection every 4 weeks Receives: Drug: sapablursen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the frequency of phlebotomy comparing Baseline with the last 20 weeks of the 37 week Treatment Period
Measured: Week 17 to Week 37
Secondary outcomes (2)
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
Measured: Week 17 to Week 37
Change in the Myeloproliferative Neoplasm Symptom Assessment Form-Total Symptom Score (MPN-SAF-TSS) From Baseline to Week 37
Measured: Baseline up to Week 37
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2021
- Study start30 Dec 2021
- Primary completion26 Jun 2025
- Study completion2 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Phlebotomy Dependent Polycythemia VeraStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05143957
- Sponsor's protocol ID
- ISIS 702843-CS4
- Other IDs
- 2021-003704-40
- Status last verified
- Jul 2026
- First submitted
- 20 Nov 2021
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/.
Publications
Palmer JM, How J, Bose P, Vachhani P, Mead AJ, Sillar J, Gerds AT, Fleischman AG, O'Neill CM, Baker RI, Hoffman R, Jung S, Ruckle JL, Yousefi K, Bhanot S, Barrett TD, Mesa RA. Sapablursen for Erythrocytosis Control in Patients with Polycythemia Vera. Blood. 2026 Aug 18:blood.2026033792. doi: 10.1182/blood.2026033792. Online ahead of print.
PubMed 42611791
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05143957
- Acronym / sponsor ID
- ISIS 702843-CS4
- Conditions
- Phlebotomy Dependent Polycythemia Vera
- Keywords
- Polycythemia Vera
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Dec 2021 (actual)
- Primary completion
- 26 Jun 2025 (actual)
- Study completion
- 2 Jun 2026 (actual)
- First posted
- 3 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sapablursen Dose Level 1 | Experimental | Drug: sapablursenSapablursen will be administered by SC injection every 4 weeks. |
| Sapablursen Dose Level 2 | Experimental | Drug: sapablursenSapablursen will be administered by SC injection every 4 weeks |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sapablursenAlso: ISIS 702843, IONIS-TMPRSS6-LRxSapablursen will be administered by SC injection. | Drug | Sapablursen Dose Level 1, Sapablursen Dose Level 2 |
Primary outcome
Change in the frequency of phlebotomy comparing Baseline with the last 20 weeks of the 37 week Treatment Period
Time frame: Week 17 to Week 37
2 secondary outcomes
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
Time frame: Week 17 to Week 37
Change in the Myeloproliferative Neoplasm Symptom Assessment Form-Total Symptom Score (MPN-SAF-TSS) From Baseline to Week 37
Time frame: Baseline up to Week 37
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2026.
- Derived from this study: PubMed 42611791Palmer JM, How J, Bose P, Vachhani P, Mead AJ, Sillar J, Gerds AT, Fleischman AG, O'Neill CM, Baker RI, Hoffman R, Jung S, Ruckle JL, Yousefi K, Bhanot S, Barrett TD, Mesa RA. Sapablursen for Erythrocytosis Control in Patients with Polycythemia Vera. Blood. 2026 Aug 18:blood.2026033792. doi: 10.1182/blood.2026033792. Online ahead of print.
- Individual participant dataSharing planned: Yes. 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/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sapablursen in people with Phlebotomy Dependent Polycythemia Vera, run by Ionis Pharmaceuticals, Inc. at 13 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Poland, Australia, United Kingdom, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the frequency of phlebotomy comparing Baseline with the last 20 weeks of the 37 week Treatment Period (time frame: Week 17 to Week 37). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05143957, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2026.