A Phase 3, Multicenter, Randomized, Double-blind Study to Compare the Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Subjects With Red Blood Cell Transfusion-dependent Anemia and Thrombocytopenia Due to IPSS Lower-risk Myelodysplastic Syndromes.

简要总结

主要结局

次要结局

• Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days(From the date of randomization of study drug up to the data cut-off date of 25 January 2019)
• Time to RBC Transfusion Independence for at Least 56 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days(From the date of randomization of study drug up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
• Duration of RBC Transfusion Reduction for Participants Who Achieved RBC Transfusion Reduction of at Least 4 Units of RBCs for at Least 8 Weeks(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
• Percentage of Participants Who Achieved RBC Transfusion Independence for ≥ 84 Days(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
• Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
• Time to RBC Transfusion Independence for at Least 84 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
• Percentage of Participants With an Erythroid Hematological Improvement (HI-E) Response According to 2006 IWG Criteria(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
• Percentage of Participants With a Hematological Improvement Response in Platelets (HI-P) According to 2006 IWG Criteria(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
• Percentage of Participants Who Achieved Platelet Transfusion Independence With a Duration of ≥ 8 Weeks (56 Days)(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
• Time to Platelet Transfusion Independence(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
• Overall Survival (OS)(From randomization up to death from any cause; up to a maximum of approximately 10 years on study; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
• Percentage of Participants With a Hematologic Response According to the 2006 IWG Criteria for MDS(Response was assessed every 3 cycles; up to the data cut-off date of 25 Jan 2019; median duration of exposure to oral azacitidine was 86.0 days and 119.0 days for placebo)
• Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML)(From randomization of study drug to the end up to final data cut-off date of 25 January 2019; maximum follow-up time was 67.9 months for azacitidine and 64.8 months for placebo group)
• Time to Progression to Acute Myeloid Leukemia (AML) Among Participants Who Progressed to AML(From randomization of study drug to progression of AML; up to a maximum of approximately 10 years on study; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
• Percentage of Participants With Significant Bleeding Events(From date of randomization until 28 days after the last dose of IP; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
• Number of Participants With Treatment Emergent Adverse Events (TEAE)(From first dose of IP up to 28 days after the last dose of IP or until the last study visit; up to a maximum of approximately 6 months on study)
• Mean Change From Baseline in the Physical Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Cycle 6(Baseline to Cycle 6 Day 1)
• Mean Change From Baseline in the Social Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
• Mean Change From Baseline in the Emotional Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
• Mean Change From Baseline in the Functional Well-Being Component of the FACT-An Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
• Mean Change From Baseline in the Anemia Subscale Within FACT-An Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
• Mean Change From Baseline in the Fatigue-Related Subscale Within the FACT-An Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
• Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index (FACT-An TOI) Summary Scale Within the FACT-An Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
• Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General (FACT-G) Summary Scale Within the FACT-An Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
• Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-Total Score at Cycle 6(Baseline to Cycle 6 Day 1)
• Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Physical Well-Being Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
• Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Social Well-Being Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
• Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Emotional Well-Being Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
• Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Functional Well-Being Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
• Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Anemia Subscale Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
• Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Fatigue Related Symptoms Subscale Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
• Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index Subscale Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
• Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General Subscale Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
• Percentage of Participants With a Clinically Meaningful Improvement (CMI) From Baseline in the Functional Assessment of Cancer Therapy Anemia-Total Score Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
• Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 2 Day 1 (C2D1)(From Baseline to Cycle 2 Day 1 (C2D1))
• Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 3 Day 1 (C3D1)(From Baseline to Cycle 3 Day 1 (C3D1))
• Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 4 Day 1 (C4D1)(From Baseline to Cycle 4 Day 1 (C4D1))
• Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 5 Day 1 (C5D1)(From Baseline to Cycle 5 Day 1 (C5D1))
• Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 6 Day 1 (C6 D1)(From Baseline to Cycle 6 Day 1 (C6 D1))
• Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 7 Day 1 (C7D1)(From Baseline to Cycle 7 Day 1 (C7D1))
• Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - End of Treatment(From Baseline to End of Treatment)
• Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level (EQ-5D-3L) Mobility Dimension Responses at Cycle 6(From Baseline to Cycle 6 Day 1)
• Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level of Self-Care Dimension Responses at Cycle 6(From Baseline to Cycle 6 Day 1)
• Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level Usual Activities Dimension Responses at Cycle 6(From Baseline to Cycle 6 Day 1)
• Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Pain/Discomfort Dimension Responses at Cycle 6(From Baseline to Cycle 6 Day 1)
• Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Anxiety/Depression Dimension Responses at Cycle 6(From Baseline to Cycle 6 Day 1)
• Healthcare Resource Utilization (HRU): Number of Participants Who Were Hospitalized(From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo)
• Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Due to Any Reason(From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo)
• Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Per Total Patient-Years(From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo)