A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
Type of trial
Interventional
(ICTRP)
Intervention under investigation
Drug: PelabresibDrug: RuxolitinibDrug: Placebo
(ICTRP)
Disease under investigation
Primary Myelofibrosis (PMF)Post-polycythemia Vera Myelofibrosis (PPV-MF)Post-essential Thrombocythemia Myelofibrosis (PET-MF)
(ICTRP)
Key Inclusion Criteria:
- Participants have diagnosis of primary myelofibrosis (PMF) or post-polycythemia vera myelofibrosis (post-PV MF) or post-essential thrombocythemia myelofibrosis (post-ET MF) according to the International Consensus Classification (ICC) of Myeloid Neoplasms and Acute Leukemias 2022
- DIPSS risk category of intermediate-1, intermediate-2 or high-risk
- Spleen volume >= 450 cm3 by CT or MRI scan (local read sufficient if no central read available)
- Have an average TSS of >=15 within 7 days prior to randomization, using MFSAF v. 4.0 (at least 4 out of 7 TSS assessments required for average calculation)
- Participants with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Blasts <5% in peripheral blood. Assessment of blasts in peripheral blood is mandatory at screening
- Platelet count >= 100 x 10^9/L in the absence of growth factors or transfusions for the previous 4 weeks
Key Exclusion Criteria:
- Prior splenectomy at any time or splenic irradiation in the previous 6 months
- Prior hematopoietic cell transplant or participant anticipated to receive a hematopoietic cell transplant within 24 weeks from the date of randomization
- Blasts >= 5% in bone marrow if results available at screening or history of accelerated phase (AP) or leukemic transformation
- History of a malignancy (other than MF, PPV-MF or PET-MF) in the past 3 years in need of systemic treatment
- Received any approved or investigational agent other than hydroxyurea or anagrelide for the treatment of MF within 14 days of first dose of study treatment or within 5 half-lives of the approved or investigational agent, whichever is longer
- Prior treatment with any JAK inhibitor or Bromodomain and extraterminal domain (BET) inhibitor
Other protocol-defined inclusion/exclusion criteria may apply.
(ICTRP)
Exclusion criteria
not available
Trial sites
United States, Argentina, Australia, China, India, Malaysia, , Switzerland, Taiwan
(ICTRP)
General Information
Novartis Pharmaceuticals
1-888-669-6682973-436-1755
novartis.email@novartis.commmackenzie@summithealth.com(ICTRP)
Academic title
A Phase 3, Randomized, Double-blind, Active-control Study of Pelabresib (DAK539) and Ruxolitinib vs. Placebo and Ruxolitinib in Adult Patients With Myelofibrosis Who Are JAK Inhibitor Naive (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
(ICTRP)
Primary and secondary end points
Number of Participants with Splenic Response (SVR35) by Central Radiology Reads at Week 24 in participants with baseline total symptom score (TSS) = 25;Absolute change from baseline in total symptom score (TSS) at Week 24 in participants with baseline TSS = 25;Number of Participants with Splenic Response (SVR35) by Central Radiology Reads at Week 24 in participants with baseline TSS = 15;Absolute change from baseline in total symptom score (TSS) at Week 24 in participants with baseline TSS = 15
(ICTRP)
Maximum observed plasma Concentration (Cmax) of pelabresib in participants enrolled in China and Japan;Number of Participants with Splenic Response (SVR35) by Central Radiology Reads over time;Absolute change from baseline and percentage change from baseline in spleen volume over time;Time to first SVR35 response;Duration of first SVR35 response;Number of Participants with TSS50 response at Week 24;Number of Participants with TSS50 response over time;Absolute and percentage change from baseline in TSS over time;Time to first TSS50 response;Duration of TSS50 response;Dual Response (SVR35 + TSS50);Hemoglobin response;Change from baseline in hemoglobin over time;Anemia response over time;Overall survival (OS);Progression-free survival (PFS);Leukemia-free survival (LFS);Exposure-Adjusted Incidence Rate (EAIR) of Participants with Leukemic Transformation;Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs);Pelabresib plasma concentrations;Time to Maximum observed plasma Concentration (Tmax) of pelabresib in participants enrolled in China and Japan;Area Under the Concentration-Time Curve over a dosing interval (AUCtau) of pelabresib in participants enrolled in China and Japan;Change from baseline over time in fatigue as measured by PROMIS SF v1.0 Fatigue 7a;Change from baseline over time in overall QOL and functional scales as measured by the EORTC QLQ-C30
(ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Novartis PharmaceuticalsNovartis PharmaceuticalsMichelle Mackenzie, novartis.email@novartis.commmackenzie@summithealth.com, 1-888-669-6682973-436-1755, Novartis Pharmaceuticals (ICTRP)
Secondary trial IDs
2025-523555-66-00, CDAK539A12303 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/study/NCT07357727 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available