A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)

The study for each participant is composed of several distinct periods: a screening period, a study treatment period, and a post-treatment follow-up phase.

1. Screening Period:

The screening period lasts for up to 28 days prior to Cycle 1 Day 1, which marks the beginning of treatment. During this time, the participant's eligibility for the study is confirmed, informed consent is obtained, and all required baseline assessments are completed. 2. Treatment Period:

The treatment period begins on Cycle 1 Day 1, which is the point of randomization and the start of study treatment. This period continues until the participant permanently discontinues study treatment, which may occur due to disease progression, unacceptable toxicity, participant withdrawal, or other reasons specified in the protocol. Throughout this period, participants receive study drugs in 21-day cycles, with pelabresib or placebo administered for 14 days and ruxolitinib given continuously. Regular site visits and assessments are conducted according to the Schedule of Activities. 3. Safety Follow-up Period:

The safety follow-up period extends for 30 days (with a window of plus or minus 3 days) after the participant receives their last dose of pelabresib or placebo. During this period, participants are monitored for any late-onset adverse events or safety concerns that may arise after discontinuing the study treatment. 4. Efficacy Follow-up Period:

Following the safety follow-up, efficacy follow-up visits are scheduled every 12 weeks for participants who have not shown evidence of disease progression, meaning there is no documented progression of splenomegaly or leukemic transformation and no new therapy for myelofibrosis has been started. The purpose of this follow-up is to continue monitoring efficacy endpoints, such as spleen imaging, laboratory assessments, and bone marrow biopsies, until either disease progression occurs or a new therapy is initiated. 5. Survival Follow-up Period:

Once a participant enters the survival follow-up phase, follow-up visits are conducted every 12 weeks and may be performed remotely. This phase applies to participants who have experienced documented disease progression or have started a new therapy for myelofibrosis. The aim of survival follow-up is to monitor overall survival and to collect ongoing data regarding disease status and any subsequent therapies the participant may receive.

• Number of Participants with Splenic Response (SVR35) by Central Radiology Reads over time [Срок оценки: Week 12, Week 36, Week 48 and every 12 weeks thereafter till End of Study (an average of 3 years)]
• Absolute change from baseline and percentage change from baseline in spleen volume over time [Срок оценки: Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)]
• Time to first SVR35 response [Срок оценки: From date of randomization to the date of first SVR35 response, assessed up to approximately 3 years]
• Duration of first SVR35 response [Срок оценки: From first SVR35 response to loss of response, assessed up to approximately 3 years]
• Number of Participants with TSS50 response at Week 24 [Срок оценки: Week 24]
• Number of Participants with TSS50 response over time [Срок оценки: Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)]
• Absolute and percentage change from baseline in TSS over time [Срок оценки: Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)]
• Time to first TSS50 response [Срок оценки: From date of randomization till date of first TSS50 response, assessed up to approximately 3 years]
• Duration of TSS50 response [Срок оценки: From first TSS50 response to loss of response, assessed up to approximately 3 years]
• Dual Response (SVR35 + TSS50) [Срок оценки: Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)]
• Hemoglobin response [Срок оценки: 12 consecutive weeks (rolling window) up to 7 days following last dose of pelabresib/placebo]
• Change from baseline in hemoglobin over time [Срок оценки: Up to 7 days following last dose of pelabresib/placebo]