臨床研究等提出・公開システム

Japanese

Date of registration	July. 01, 2026
Last modified on	July. 01, 2026
Trial ID	jRCT2011260023

Scientific 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 (CDAK539A12303)
Public Title	A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF) (MANIFEST-3) (CDAK539A12303)

Contact for Scientific Queries	Name	Yamauchi Kyosuke
	Affiliation	Novartis Pharma. K.K.
	Address	Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan
	Telephone	+81-120-003-293
	E-mail	rinshoshiken.toroku2@novartis.com
Contact for Public Queries	Name	Yamauchi Kyosuke
	Affiliation	Novartis Pharma. K.K.
	Address	Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan
	Telephone	+81-120-003-293
	E-mail	rinshoshiken.toroku2@novartis.com

Recruitment status	Pending

Anticipated date of first enrollment		Sept. 01, 2026
Target sample size		16
Study Type		Interventional
Study Design	allocation	randomized controlled trial
	masking	double blind
	control	placebo control
	assignment	parallel assignment
	purpose	treatment purpose
Key inclusion & exclusion criteria	Inclusion Criteria	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
	Exclusion Criteria	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.
	Age Minimum	18age old over
	Age Maximum	No limit
	Gender	Both
Health Condition(s) or Problem(s) Studied		Myelofibrosis
Intervention(s)		Arm 1: Pelabresib + Ruxolitinib: Pelabresib (DAK539) orally once daily for 14 days of each 21-day cycle + Ruxolitinib orally twice daily throughout each cycle Arm 2: Placebo + Ruxolitinib: Placebo orally once daily for 14 days of each 21-day cycle + Ruxolitinib orally twice daily throughout each cycle
Primary Outcome(s)		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

Primary Sponsor	Novartis Pharma. K.K.

Secondary Sponsor

Name of Certified Review Board	Sapporo Medical Association's Institutional Review Board
Address	1-1, Odori Nishi 19-chome, Chuo-ku, Sapporo-shi, Hokkaido, 060-0042, Japan, Hokkaido
Approval Status	Approval
Date of approval	June. 11, 2026

Plan to share IPD	Yes
Plan description	Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Plan to share IPD

Yes

Plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Secondary ID(s)	NCT07357727
Issuing Authority	Clinical Trials.gov

Countries of Recruitment（Except Japan）	US/South Korea/Switzerland