Clinical trial NCT05143957: A Study to Evaluate Sapablursen (Formerly ISIS 702843, IONIS-TMPRSS6-LRx) in Patients With Polycythemia Vera
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Phlebotomy Dependent Polycythemia Vera
Keywords: Polycythemia Vera
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-03
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in the frequency of phlebotomy comparing Baseline with the last 20 weeks of the 37 week Treatment Period
timeFrame: Week 17 to Week 37
Secondary outcomes:
measure: 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
timeFrame: Week 17 to Week 37
measure: Change in the Myeloproliferative Neoplasm Symptom Assessment Form-Total Symptom Score (MPN-SAF-TSS) From Baseline to Week 37
timeFrame: Baseline up to Week 37
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: O'Neal Comprehensive Cancer Center University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Norris Comprehensive Cancer Center
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Waratah
country: Australia
facility: Calvary Mater Newcastle Hospital
state: New South Wales
city: Albury
country: Australia
facility: Border Medical Oncology Research Unit
city: West Perth
country: Australia
facility: The Perth Blood Institute
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie, Klinika Hematoonkologii i Transplantacji Szpiku
city: Słupsk
country: Poland
facility: Wojewódzki Szpital Specjalistyczny Sp. z o.o.
city: Toruń
country: Poland
facility: MICS Centrum Medyczne Toruń
city: Lincoln
country: United Kingdom
facility: United Lincolnshire Hospitals NHS Trust
state: England
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: West Bromwich
country: United Kingdom
facility: Sandwell and West Birmingham Hospitals NHS Trust
Study officials:
References: