A Phase 2a, Randomized, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of sapablursen (ISIS 702843-CS4) Administered to Patients with Phlebotomy Dependent Polycythemia Vera (PD-PV)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ionis Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

21 Jun 2023 → ongoing

Decision date (initial)

2024-07-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ionis Pharmaceuticals Inc.

External identifiers

EU CT number

2024-512482-14-00

EudraCT number

2021-003704-40

WHO UTN

U1111-1305-1088

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Efficacy, Others, Safety

Evaluate the efficacy of sapablursen to reduce the frequency of phlebotomy throughout the last 20 weeks of the Treatment Period

Secondary objectives 7

1. Evaluate the efficacy of sapablursen to decrease the frequency of phlebotomy by various thresholds throughout the last 20 weeks of the Treatment Period
2. Evaluate the efficacy of sapablursen to improve the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score (TSS) at Week 37
3. Safety Objective: Evaluate the safety and tolerability of multiple doses of sapablursen i patients with PD-PV through Week 73
4. Exploratory Objectives: Evaluate the efficacy of sapablursen to control Hct without phlebotomy throughout the last 20 weeks of the Treatment Period
5. Exploratory Objectives: Evaluate the efficacy of sapablursen to reduce the frequency of phlebotomy from Week 37 to 73 of the Treatment Extension Period
6. Exploratory Objectives: Evaluate the efficacy of sapablursen to control Hct without phlebotomy from Week 37 to 73 of the Treatment Extension Period
7. PK Objectives: Evaluate PK exposure over time and potential PK/PD correlation on relevant biomarkers and efficacy outcome measures

Conditions and MedDRA coding

Polycythemia Vera

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

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. Patients 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 treated with the cytoreductive therapy it must have been discontinued at least 3 months prior to Screening. If patients are currently on cytoreductive therapy they must be on a stable dose for at least 3 months prior to Screening.

Exclusion criteria 8

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 nonmetastatic prostate cancer that has been successfully treated
8. Surgery requiring general anesthesia within 1 month prior to Screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Reduction in the frequency of phlebotomy comparing Baseline with the last 20 weeks of the 37-week Treatment Period

Secondary endpoints 7

1. 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 ]
2. 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 ]
3. Safety Endpoint: AEs, vital signs, clinical laboratory tests (serum chemistry, hematology, urinalysis, coagulation panel, thyroid panel [TSH, T3, T4], electrocardiogram [ECG]
4. Exploratory Endpoints: Proportion of patients achieving Hct control (i.e. Hct<45%) without receiving phlebotomy throughout the last 20 weeks of the 37-week Treatment Period
5. Exploratory Endpoints: Reduction in the frequency of phlebotomy comparing Baseline to the last 36 Weeks of the Treatment Extension Period
6. Exploratory Endpoints: Proportion of patients achieving Hct control (i.e., Hct<45%) without receiving phlebotomy from Week 37 to 73 of the Treatment Extension Period
7. PK Endpoint: A PK profile including pre-dose, 1,2,4, and optional 6-hour samples will be collected at Day 1. A PK profile will also be collected at Week 25 and will include: pre-dose, 1-, 2-, and 3-hour samples. Trough levels will be evaluated at all clinic visits at will not be required for hom health care visits.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ionis Pharmaceuticals Inc.

Sponsor organisation

Ionis Pharmaceuticals Inc.

Address

2855 Gazelle Court

City

Carlsbad

Postcode

92010-6670

Country

United States

Scientific contact point

Organisation

Ionis Pharmaceuticals Inc.

Contact name

Ionis Pharmaceutical Inc.

Public contact point

Organisation

Ionis Pharmaceuticals Inc.

Contact name

Ionis Pharmaceutical Inc.

Third parties 8

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications