Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Momelotinib · 9 trials · 12 indications
Myelofibrosis Symptom Assessment Form (MFSAF) TSS version (v) 4.0 response rate was defined as percentage of participants with a \>= 50 percent (%) reduction from Baseline in mean MFSAF TSS over consecutive 28-day period immediately before end of Week 24. TSS response rate was measured using MFSAF v4.0. MFSAF v4.0 comprises 7 domains representing 7 most relevant symptoms of myelofibrosis (MF) identified through existing participant and clinician-based evidence: fatigue,night sweats,pruritus,abdominal discomfort,pain under left ribs,early satietyand bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0(absent) to 10(worst imaginable). The MFSAF TSS was calculated as sum of scores of 7 domains for a possible range of scores of 0 to 70, with a higher TSS corresponding to more severe symptoms. A reduction from Baseline corresponded to a lessening of MF symptoms. Baseline was the last assessment done before or on the day of first dose date.
Splenic response rate at Week 24 is defined as the percentage of participants who achieved a spleen volume reduction of ≥ 35% from baseline at the Week 24 assessment as measured by MRI or CT.
ORR is defined as the proportion of participants who have achieved complete response (CR) or partial response (PR) during the 26-week Primary Treatment Period.
RBC-TI defined as not requiring RBC transfusions (except in the case of clinically overt bleeding). Percentage of participants with RBC-TI will be measured for any consecutive 12-week interval over 24-week duration.
TI response is defined as not requiring red blood cell (RBC) transfusion (except in the case of clinically overt bleeding) for any ≥12-week interval.
Long-term safety and tolerability profile of momelotinib based on safety data (adverse events and selected hematology and chemistry laboratory parameters) collected after the first dose of momelotinib in the parent study.
Measured by complete response (CR) rate, partial response (PR) rate and clinical improvement (CI) rate according to IWG-MRT consensus criteria
| Arm | Type | Description |
|---|---|---|
| Momelotinib | EXPERIMENTAL | Participants will receive momelotinib plus placebo to match danazol |
| Danazol | ACTIVE_COMPARATOR | Participants will receive danazol plus placebo to match momelotinib |
| Arm 1: Momelotinib | EXPERIMENTAL | Participants will receive open-label momelotinib for 24 weeks during the randomized treatment phase, after which they will be eligible to receive momelotinib in an extended treatment phase for up to an additional 204 weeks. |
| Arm 2: Best Available Therapy (BAT) | ACTIVE_COMPARATOR | Participants in the BAT treatment arm will receive open-label treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may be changed at any time during the study except during the screening period. After completion of the randomized treatment phase, participants will be eligible to receive momelotinib for the duration of the study during the extended treatment phase for up to 204 weeks. |
| Ruxolitinib | ACTIVE_COMPARATOR | Participants will receive ruxolitinib plus placebo to match momelotinib. |
| Momelotinib Dose level 1 + Glucocorticoids | EXPERIMENTAL | Participants will receive momelotinib at dose level 1 along with glucocorticoids as a background therapy (prednisone or prednisolone). Due to adaptive design of the study, additional participants may be randomized to this arm in phase 3. |
| Momelotinib Dose level 2 + Glucocorticoids | EXPERIMENTAL | Participants will receive momelotinib at dose level 2 along with glucocorticoids as a background therapy (prednisone or prednisolone). Due to adaptive design of the study, additional participants may be randomized to this arm in phase 3 |
| Placebo + Glucocorticoids | PLACEBO_COMPARATOR | Participants will receive momelotinib matched placebo along with glucocorticoids as a background therapy(prednisone or prednisolone). Due to adaptive design of the study, additional participants may be randomized to this arm in phase 3 |
| Momelotinib dose level 1 | EXPERIMENTAL | - |
| Momelotinib dose level 2 | EXPERIMENTAL | - |
| Momelotinib + Luspatercept | EXPERIMENTAL | Participants with transfusion dependent primary myelofibrosis or post- PV/ ET myelofibrosis that is JAKi naïve or JAKi experienced will receive momelotinib and luspatercept. |
| Cohort 1 | EXPERIMENTAL | Participants previously enrolled in Study CCL09191E will receive momelotinib for approximately 4 years. |
| Cohort 2 | EXPERIMENTAL | Participants previously enrolled in Study YM387-II-02 will receive momelotinib for approximately 4 years. |
| Cohort 3 | EXPERIMENTAL | Participants previously enrolled in Study GS-US-354-0101 will receive momelotinib for up to 4 years. Cohort 3 was closed and all enrolled participants were discontinued from this study because parent Study GS-US-354-0101 was terminated. |
| Cohort 4 | EXPERIMENTAL | Participants previously enrolled in Study GS-US-352-1672 will receive momelotinib for approximately 4 years. |
| Name | Type | Description |
|---|---|---|
| Momelotinib | DRUG | Momelotinib tablets will be self-administered orally once daily |
| Placebo to match danazol | DRUG | Danazol placebo capsules will be self-administered orally twice daily |
| Danazol | DRUG | Danazol capsules will be self-administered orally twice daily |
| Placebo to match momelotinib | DRUG | Momelotinib placebo tablets will be self-administered orally once daily |
| Best Available Therapy (BAT) | DRUG | Regimens for BAT may include but are not limited to chemotherapy (eg hydroxyurea), anagrelide, corticosteroid, hematopoietic growth factor, immunomodulating agent, androgen, interferon, and may include no myelofibrosis treatment. |
| Ruxolitinib | DRUG | Ruxolitinib tablets administered orally twice daily |
| Placebo to match ruxolitinib | DRUG | Placebo to match ruxolitinib tablets administered orally twice daily |
| Glucocorticoids | DRUG | Glucocorticoids (prednisone or prednisolone) will be administered |
| Placebo | DRUG | Placebo will be administered |
| Luspatercept | DRUG | Luspatercept will be administered subcutaneously. |
Inclusion Criteria: * Age \>= 18 years. * Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) 2016 criteria, or Post- polycythemia vera/essential thrombocythemia (PV/ET) MF in accordance with the International Working Group-Myeloproliferative Neoplasms Research and Tre...