A Phase 3, Randomized, Double-blind, Add-on Study Evaluating the Safety and Efficacy of Navtemadlin Plus Ruxolitinib vs Placebo Plus Ruxolitinib in Patients with Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib

Conditions

Primary Myelofibrosis, Secondary Myelofibrosis (including but not limited to myelofibrosis post-Polycythemia Vera or post-Essential Thrombocythemia)

Brief summary

SVR will be evaluated 24 weeks after randomized treatment begins by MRI/CT scan (central review)., TSS reduction will be evaluated 24 weeks after randomized treatment begins using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.

Detailed description

The proportion of patients who have spleen volume reduction between Arm 1 and Arm 2, The proportion of patients who have TSS reduction between Arm 1 and Arm 2, Time to death from any cause in patients randomized to each arm, Time to progression or death from any cause in patients randomized to each arm, Analyses of the safety endpoints will include the following measurements or assessments: physical examinations, laboratory tests, adverse events (AEs), serious AEs (SAEs), electrocardiograms (ECGs), and vital signs, Change in SVR 24 weeks after the randomized treatment begins, Change in TSS 24 weeks after the randomized treatment begins

Vachhani P, Yacoub A, Rampal R, Bradley T, Harrison C, Jain T, Kuykendall A, Palandri F, Mascarenhas J, Al-Ali H, Passamonti F, Rothbaum W, Verstovsek S, Heidel FH.

2026-03-07

10.1080/14796694.2026.2638989

Interventions

DRUGONDANSETRON

DRUGNavtemadlin 25-120

DRUGNavtemadlin (KRT-232)

DRUGPlacebo to match navtemadlin 30mg

DRUGfilm-coated tablet

DRUGPlacebo to match ondansetron

DRUGcapsule

DRUGLOPERAMID WZF

DRUG2 mg

DRUGtabletki

DRUGPlacebo to match EU-sourced loperamide

DRUGRUXOLITINIB

DRUGPlacebo to match navtemadlin 120mg

DRUGNavtemadlin 25-30

DRUGNavtemadlin 25-60

DRUGLOPERAMIDE HYDROCHLORIDE

DRUGPlacebo to match navtemadlin 60mg

DRUGPlacebo to match US-sourced loperamide

DRUGPlacebo to match navtemadlin 180mg

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Design outcomes

Primary

Measure	Time frame
SVR will be evaluated 24 weeks after randomized treatment begins by MRI/CT scan (central review)., TSS reduction will be evaluated 24 weeks after randomized treatment begins using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.	—

Secondary

Measure	Time frame
The proportion of patients who have spleen volume reduction between Arm 1 and Arm 2, The proportion of patients who have TSS reduction between Arm 1 and Arm 2, Time to death from any cause in patients randomized to each arm, Time to progression or death from any cause in patients randomized to each arm, Analyses of the safety endpoints will include the following measurements or assessments: physical examinations, laboratory tests, adverse events (AEs), serious AEs (SAEs), electrocardiograms (ECGs), and vital signs, Change in SVR 24 weeks after the randomized treatment begins, Change in TSS 24 weeks after the randomized treatment begins	—

Measure

Time frame

The proportion of patients who have spleen volume reduction between Arm 1 and Arm 2, The proportion of patients who have TSS reduction between Arm 1 and Arm 2, Time to death from any cause in patients randomized to each arm, Time to progression or death from any cause in patients randomized to each arm, Analyses of the safety endpoints will include the following measurements or assessments: physical examinations, laboratory tests, adverse events (AEs), serious AEs (SAEs), electrocardiograms (ECGs), and vital signs, Change in SVR 24 weeks after the randomized treatment begins, Change in TSS 24 weeks after the randomized treatment begins

—

Countries

Austria, Belgium, Croatia, Czechia, France, Germany, Greece, Hungary, Italy, Poland, Portugal, Romania, Spain

Outcome results

None listed