Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Number of Participants With Dose-limiting Toxicities (DLTs) |
DLTs were defined as the occurrence of any protocol-defined toxicities occurring up to and including Day 28, except those with a clear alternative explanation (e.g., disease progression, other medications) or transient (= 72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 criteria. |
up to Day 28 |
|
| Primary |
Change From Baseline in Spleen Volume Through Week 12 of the Initial Study Period as Measured by Magnetic Resonance Imaging (MRI) (or Computed Tomography [CT] Scan in Applicable Participants) |
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
Baseline; Week 12 |
|
| Primary |
Percent Change From Baseline in Spleen Volume Through Week 12 as Measured by MRI (or CT Scan in Applicable Participants) |
Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] / Baseline value) x 100. |
Baseline; Week 12 |
|
| Secondary |
Change From Baseline in Spleen Volume Through Week 24 of the Initial Study Period as Measured by MRI (or CT Scan in Applicable Participants) |
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
Baseline; Week 24 |
|
| Secondary |
Percent Change From Baseline in Spleen Volume Through Week 24 as Measured by MRI (or CT Scan in Applicable Participants ) |
Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] / Baseline value) x 100. |
Baseline; Week 24 |
|
| Secondary |
Change From Baseline in the Total Symptom Score (TSS) Through Week 12 as Measured by Myelofibrosis Symptom Assessment Form (MFSAF) Version 3.0 (v3.0) Symptom Diary |
The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total scores from the last 7 days before the first dose of INCB050465. The Week 12 TSS was the average of the daily total scores from the last 7 consecutive days before the Week 12 visit. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
Baseline; Week 12 |
|
| Secondary |
Percent Change From Baseline in the TSS Through Week 12 as Measured by MFSAF v3.0 Symptom Diary |
The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total scores from the last 7 days before the first dose of INCB050465. The Week 12 TSS was the average of the daily total scores from the last 7 consecutive days before the Week 12 visit. Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] / Baseline value) x 100. |
Baseline; Week 12 |
|
| Secondary |
Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary |
The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total scores from the last 7 days before the first dose of INCB050465. The Week 24 TSS was the average of the daily total scores from the last 7 consecutive days before the Week 24 visit. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
Baseline; Week 24 |
|
| Secondary |
Percent Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary |
The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total scores from the last 7 days before the first dose of INCB050465. The Week 24 TSS was the average of the daily total scores from the last 7 consecutive days before the Week 24 visit. Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] / Baseline value) x 100. |
Baseline; Week 24 |
|
| Secondary |
Change From Baseline in the TSS Through Week 12 as Measured by Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) |
The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
Baseline; Week 12 |
|
| Secondary |
Percent Change From Baseline in the TSS Through Week 12 as Measured by MPN-SAF |
The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] / Baseline value) x 100. |
Baseline; Week 12 |
|
| Secondary |
Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF |
The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
Baseline; Week 24 |
|
| Secondary |
Percent Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF |
The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] / Baseline value) x 100. |
Baseline; Week 24 |
|
| Secondary |
Number of Participants With the Indicated Patient Global Impression of Change (PGIC) Score at Week 12, Week 24, and the End of Treatment (EOT) |
The PGIC questionnaire consists of a single question with 7 possible answers: "Since the start of treatment you've received in this study, your myelofibrosis symptoms are: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse." |
Baseline; up to 1494 days (EOT) |
|
| Secondary |
Mean PGIC Score at Week 12, Week 24, and the EOT |
The PGIC questionnaire consists of a single question with 7 possible answers: "Since the start of treatment you've received in this study, your myelofibrosis symptoms are: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse." |
up to 1494 days (EOT) |
|
| Secondary |
Best Overall Response (Percentage of Participants With Complete Response [CR] or Partial Response [PR]) for Investigator-Reported International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Response Assessment |
A participant was considered as a responder if the participant had a best overall response of CR or PR. CR: (a) bone marrow (BM): age-adjusted normocellularity (AAN); < 5% blasts; = grade 1 myelofibrosis (MF); (b) peripheral blood (PD): hemoglobin (Hg) = 100 grams per Liter (g/L) and < upper normal limit (UNL); neutrophils = 1 × 10^9/L and < UNL; (c) platelets = 100 × 10^9/L and < UNL; < 2% immature myeloid cells (IMCs); (d) clinical: resolution of disease symptoms; spleen/liver not palpable; no extramedullary hematopoiesis (EMH). PR: (a) PB: Hg = 100 g/L and < UNL; neutrophils = 1 × 10^9/L and < UNL; platelets = 100 × 10^9/L and < UNL; < 2% IMCs; (b) clinical: resolution of disease symptoms; spleen/liver not palpable; no EMH; (c) BM: AAN; < 5% blasts; = Grade 1 MF; and PB: Hg = 85 g/L but < 100 g/L and < UNL; neutrophils = 1 × 10^9/L and < UNL; platelets = 50 × 10^9/L but < 100 × 10^9/L and < UNL; < 2% IMCs. |
Week 12 and every 12 weeks thereafter (up to 1494 days [EOT]) |
|
| Secondary |
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) |
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or requird changes in the study drug(s). TEAEs were defined as AEs that began or worsened from Baseline after the first administration of study drug. |
up to approximately 4 years |
|
| Secondary |
Number of Participants With Any TEAE During the Transition Period |
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or requird changes in the study drug(s). TEAEs were defined as AEs that began or worsened from Baseline after the first administration of study drug. Participants who had been assigned to dosing arms with weekly dosing beyond Week 8 had the opportunity to transition to all daily dosing at 5 mg if agreed upon by the participant and the Investigator. |
up to approximately 4 years |
|
| Secondary |
Cmax of Parsaclisib |
Cmax was defined as the maximum observed plasma concentration. |
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
Tmax of Parsaclisib |
tmax was defined as the time to the maximum concentration. |
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
Cmin of Parsaclisib |
Cmin was defined as the minimum observed plasma concentration. |
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
AUC0-4h of Parsaclisib |
AUC0-4h was defined as the area under the plasma concentration-time curve from time = 0 to 4 hours post-dose. |
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
AUC0-t of Parsaclisib |
AUC0-t was defined as the area under the plasma concentration-time curve from time =0 to the last measurable concentration at time = t. |
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
Clast of Parsaclisib |
Clast was defined as the last quantifiable concentration. |
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
Tlast of Parsaclisib |
tlast was defined as the time of the last quantifiable concentration. |
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
Cmax of Ruxolitinib |
Cmax was defined as the maximum observed plasma concentration. |
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
Tmax of Ruxolitinib |
tmax was defined as the time to the maximum concentration. |
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
Cmin of Ruxolitinib |
Cmin was defined as the minimum observed plasma concentration. |
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
AUC0-4h of Ruxolitinib |
AUC0-4h was defined as the area under the plasma concentration-time curve from time = 0 to 4 hours post-dose. |
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
AUC0-t of Ruxolitinib |
AUC0-t was defined as the area under the plasma concentration-time curve from time =0 to the last measurable concentration at time = t. |
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
Clast of Ruxolitinib |
Clast was defined as the last quantifiable concentration. |
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
| Secondary |
Tlast of Ruxolitinib |
tlast was defined as the time of the last quantifiable concentration. |
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose |
|
