PACIFICA: A Phase 3 Study of Pacritinib in Patients with Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sobi Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

24 Jul 2020 → ongoing

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Sobi Inc. USA

External identifiers

EU CT number

2024-515953-52-00

EudraCT number

2020-000111-69

WHO UTN

U1111-1312-0648

ClinicalTrials.gov

NCT03165734

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Pharmacodynamic

1. To compare the efficacy of pacritinib with that of physician’s choice (P/C) therapy, as assessed by the proportion of participants achieving a ≥35% spleen volume reduction (SVR) from baseline at Week 24 as measured by magnetic resonance imaging (MRI; preferred) or computed tomography (CT) scans
2. To compare the efficacy of pacritinib with P/C therapy, as assessed by the proportion of participants achieving a ≥50% reduction in Total Symptom Score (TSS) from baseline at Week 24

Secondary objectives 3

1. 1. To compare the percentage of participants who self-assess as “very much improved” or “much improved” as measured by the Patient Global Impression of Change (PGIC) in participants treated with pacritinib versus those treated with P/C
2. 2. To compare the overall survival (OS) of participants treated with pacritinib versus those treated with P/C
3. 3. To compare the safety of pacritinib versus P/C therapy

Conditions and MedDRA coding

Post-Essential Thrombocythaemia Myelofibrosis

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to patient level data and related study documents. Patient level data will be anonymized and study documents, if applicable will be redacted to protect the privacy of trial participants. Further details on Sponsor's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.sobi.com/en/policies

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 1. Primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF
2. 2. Platelet count of <50,000/μL at Screening (Day -35 to Day -3)
3. 3. Dynamic International Prognostic Scoring System Intermediate-1, Intermediate-2, or High-Risk
4. 4. Palpable splenomegaly ≥5 cm below the lower costal margin in the midclavicular line as assessed by physical examination
5. 5. TSS of ≥10 on the MPN-SAF TSS 2.0 or a single symptom score of ≥5 or two symptoms of ≥3, including only the symptoms of left upper quadrant pain, bone pain, itching, or night sweats. The TSS criteria need only to be met on a single day
6. 6. Age ≥18 years
7. 7. Eastern Cooperative Oncology Group performance status 0 to 2
8. 8. Peripheral blast count of <10% throughout the Screening period prior to randomization
9. 9. Absolute neutrophil count of ≥500/μL
10. 10. Left ventricular cardiac ejection fraction of ≥50% by echocardiogram or multigated acquisition scan
11. 11. Adequate liver and renal function, defined by liver transaminases (aspartate aminotransferase [AST]/serum glutamic-oxaloacetic transaminase [SGOT] and alanine aminotransferase [ALT]/serum glutamic pyruvic transaminase [SGPT]) ≤3 × the upper limit of normal (ULN) (AST/ALT ≤5 × ULN if transaminase elevation is related to MF), total bilirubin ≤4 × ULN (in cases where total bilirubin is elevated, direct bilirubin ≤4 × ULN is required), and creatinine ≤2.5 mg/dL
12. 12. Adequate coagulation defined by prothrombin time/international normalized ratio and partial thromboplastin time ≤1.5 × ULN
13. 13. If fertile, willing to use highly effective birth control methods during the trial
14. 14. Willing to undergo and able to tolerate frequent MRI or CT scan assessments during the study
15. 15. Able to understand and willing to complete symptom assessments using a patient-reported outcome instrument
16. 16. Provision of signed informed consent

Exclusion criteria 31

1. 1. Life expectancy <6 months
2. 2. Completed allogeneic stem cell transplant, or are eligible for and willing to complete other approved available therapy including allogeneic stem cell transplant
3. 3. History of splenectomy or planning to undergo splenectomy
4. 4. Splenic irradiation within the last 6 months
5. 5. Previously treated with pacritinib
6. 6. Treatment with any MF-directed therapy within 14 days prior to treatment Day 1
7. 7. Prior treatment with more than one JAK2 inhibitor
8. 8. Prior treatment with ruxolitinib, if BOTH of the following conditions are met: i. exposure to higher-dose ruxolitinib (>10 mg daily) within 120 days prior to treatment Day 1; AND ii. total duration of treatment with higher-dose ruxolitinib (>10 mg daily) was >90 days, from first to last exposure (i.e., this 90-day period starts on the date of first administration of ruxolitinib at a total daily dose of >10 mg and continues for 90 calendar days, regardless of whether higher-dose ruxolitinib is administered continuously or intermittently
9. 9. Prior treatment with any JAK2 inhibitor other than ruxolitinib, irrespective of dose, with a duration of >90 days. The 90-day period starts on the date of first administration of JAK2 inhibitor therapy and continues for 90 calendar days, regardless of whether therapy is administered continuously or intermittently
10. 10. Treatment with an experimental therapy, including MF-directed experimental therapies within 28 days prior to treatment Day 1
11. 11. Systemic treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or a strong CYP3A4 inducer within 14 days prior to treatment Day 1. Shorter washout periods may be permitted after consultation with the Medical Monitor, provided that the washout period is at least five half-lives of the drug prior to treatment Day 1
12. 12. Significant recent bleeding history defined as National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2 within 3 months prior to treatment Day 1, unless precipitated by an inciting event (eg, surgery, trauma, or injury)
13. 13. Systemic treatment with medications that increase the risk of bleeding, including anticoagulants, antiplatelet agents (except for aspirin dosages of ≤100 mg per day), and daily use of cyclooxygenase-1 (COX-1) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) within 14 days prior to treatment Day 1. Treatment with systemic anti-vascular endothelial growth factor (anti-VEGF) agents within 28 days prior to treatment Day 1.
14. 14. Systemic treatment with medications that can prolong the QT interval within 14 days prior to treatment Day 1. Shorter washout periods may be permitted after consultation with the Medical Monitor, provided that the washout period is at least five half-lives of the drug prior to treatment Day 1
15. 15. Any history of CTCAE grade ≥2 non-dysrhythmia cardiac conditions within 6 months prior to treatment Day 1. Patients with asymptomatic grade 2 non-dysrhythmia cardiovascular conditions may be considered for inclusion, after consultation with the Medical Monitor, if stable and unlikely to affect patient safety
16. 16. Any history of CTCAE grade ≥2 cardiac dysrhythmias within 6 months prior to treatment Day 1. Patients with non-corrected QT interval CTCAE grade 2 cardiac dysrhythmias may be considered for inclusion, after consultation with the Medical Monitor, if the dysrhythmias are stable, asymptomatic, and unlikely to affect patient safety
17. 17. QT corrected by the Fridericia method (QTcF) prolongation >450 ms or other factors that increase the risk for QT interval prolongation (eg, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], or history of long QT interval syndrome)
18. 18. New York Heart Association Class II, III, or IV congestive heart failure
19. 19. Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication
20. 20. Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn’s Disease, inflammatory bowel disease, chronic diarrhea, or chronic constipation
21. 21. Other malignancy within 3 years prior to treatment Day 1. The following patients may be eligible despite having had a malignancy within the prior 3 years: patients with curatively treated squamous or basal cell carcinoma of the skin; patients with curatively treated non-invasive cancers; patients with organ-confined prostate cancer with prostate specific antigen (PSA) <20 ng/mL and National Comprehensive Cancer Network risk of Very Low, Low, or Favorable Intermediate; and patients with curatively treated non-metastatic prostate cancer with negative PSA
22. 22. Uncontrolled intercurrent illness, including, but not limited to, ongoing active infection, psychiatric illness, or social situation that, in the judgment of the Investigator, would limit compliance with trial requirements
23. 23. Known seropositivity for human immunodeficiency (HIV) virus. For patients in Czech Republic, France, and Italy only: testing for HIV is required during Screening
24. 24. Known active hepatitis A, B, or C virus infection. For patients in Czech Republic, France, and Italy only: testing for hepatitis B and C is required during Screening
25. 25. Women who are pregnant or lactating
26. 26. Concurrent enrollment in another interventional trial
27. 27. Severe thrombocytopenia due to vitamin B12 deficiency, folate deficiency, or viral infection in the opinion of the investigator
28. 28. Known hypersensitivity to pacritinib or any of the following inactive ingredients: microcrystalline cellulose, polyethylene glycol, and magnesium stearate; any contraindication to the “physician’s choice” medicinal product selected by the investigator to be used as the comparator or to loperamide or equivalent antidiarrheal medication
29. 29. Persons deprived of their liberty by a judicial or administrative decision
30. 30. Persons subject to legal protection measures or unable to express their consent
31. 31. Temporarily incapacitated persons

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Percentage of participants who achieve at least 35% reduction in spleen volume from baseline as measured by MRI (preferred) or CT scan at Week 24.
2. 2. Percentage of participants with at least 50% reduction in TSS from baseline at Week 24 (as defined by the Myeloproliferative Neoplasm Symptom Assessment Form [MPN‐SAF TSS 2.0] excluding the “tiredness” component)

Secondary endpoints 3

1. 1. Percentage of participants who self-assess as “very much improved” or “much improved” at Week 24
2. 2. Time from randomization to the date of death due to any cause
3. 3. Incidence and severity of TEAEs, including SAEs and deaths, as well as laboratory values and vital signs, including cardiac evaluations from the time of randomization until 30 days after completion of treatment with pacritinib and/or physician's choice therapy

Investigational products

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

Test 1

Comparator 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sobi Inc.

Sponsor organisation

Sobi Inc.

Address

77 4th Avenue Floor 3

City

Waltham

Postcode

02451-7567

Country

United States

Scientific contact point

Organisation

Sobi Inc.

Contact name

Medical Information

Public contact point

Organisation

Sobi Inc.

Contact name

Medical Information

Third parties 12

Locations

8 EU/EEA countries · 58 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 81 files

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

Application history

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