A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
Tipo di studio
Interventional
(ICTRP)
Intervento studiato
Drug: PelabresibDrug: RuxolitinibDrug: Placebo
(ICTRP)
Malattie studiate
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)
Criteri di esclusione
non disponibile
Luogo dello studio
Stati Uniti, Argentina, Australia, China, India, Malesia, , Svizzera, Taiwan
(ICTRP)
Informazioni generali
Novartis Pharmaceuticals
1-888-669-6682973-436-1755
novartis.email@novartis.commmackenzie@summithealth.com(ICTRP)
Titolo accademico
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)
Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
(ICTRP)
Endpoint primari e secondari
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)
Data di registrazione
non disponibile
Inclusione del primo partecipante
non disponibile
Sponsor secondari
non disponibile
Contatti aggiuntivi
Novartis PharmaceuticalsNovartis PharmaceuticalsMichelle Mackenzie, novartis.email@novartis.commmackenzie@summithealth.com, 1-888-669-6682973-436-1755, Novartis Pharmaceuticals (ICTRP)
ID secondari
2025-523555-66-00, CDAK539A12303 (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT07357727 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile