Pelabresib + Ruxolitinib for Myelofibrosis

(MANIFEST-3 Trial)

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: JAK inhibitors, BET inhibitors

Disqualifiers: Splenectomy, Hematopoietic transplant, Malignancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 25

Duration: Variable (until discontinuation)

460 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this trial is to evaluate whether treatment with pelabresib in combination with ruxolitinib leads to improved clinical outcomes compared to ruxolitinib alone in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF) who have not previously received Janus kinase (JAK) inhibitor therapy.

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Inclusion Criteria

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)

Platelet count ≥ 100 x 10^9/L in the absence of growth factors or transfusions for the previous 4 weeks

I have less than 5% blasts in my blood.

Exclusion Criteria

I have had my spleen removed or had spleen radiation in the last 6 months.

I have at least 5% blasts in my bone marrow or a history of advanced leukemia.

I have not taken any MF treatments (except hydroxyurea or anagrelide) recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive pelabresib or placebo for 14 days and ruxolitinib continuously in 21-day cycles until discontinuation due to various reasons.

Variable (until discontinuation)

Regular site visits and assessments according to the Schedule of Activities

Safety Follow-up

Participants are monitored for late-onset adverse events or safety concerns after discontinuing study treatment.

4 weeks

1 visit (in-person or virtual)

Efficacy Follow-up

Participants are monitored for efficacy endpoints every 12 weeks if no disease progression is observed.

Every 12 weeks until disease progression or new therapy

Visits every 12 weeks

Survival Follow-up

Participants are monitored for overall survival and disease status every 12 weeks after disease progression or new therapy.

Every 12 weeks

Remote visits every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pelabresib
• Ruxolitinib

How Is the Trial Designed?

Group I: Arm 1: Pelabresib + Ruxolitinib Experimental Treatment 2 Interventions

Participants in this arm receive pelabresib (DAK539) orally once daily for 14 days of each 21-day cycle, in combination with ruxolitinib, which is taken orally twice daily throughout each cycle. Participants may continue receiving study treatment until they experience unacceptable toxicity, disease progression, or until either the investigator or the participant decides to discontinue treatment.

Group II: Arm 2: Placebo + Ruxolitinib Placebo Group 2 Interventions

Participants in this arm receive a matching placebo orally once daily for 14 days of each 21-day cycle, together with ruxolitinib, which is also taken orally twice daily throughout each cycle. Participants may continue receiving study treatment until they experience unacceptable toxicity, disease progression, or until either the investigator or the participant decides to discontinue treatment.

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD