The primary objective of this study is to compare the effect of mitapivat versus placebo on transfusion burden in pediatric participants with α- or β-transfusion-dependent thalassemia.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
54
Tablets or Granules
Tablets or Granules
Percentage of Participants Who Achieved Transfusion Reduction Response (TRR) Through Week 48
TRR is defined as ≥50 percent (%) reduction in transfused red blood cells (RBC) volume (normalized by weight) in any consecutive 12-week period through Week 48 compared with historical RBC transfusion volume (normalized by weight) and standardized to 12 weeks.
Time frame: Baseline, through Week 48
Percentage of Participants Who Achieved TRR2 From Week 13 to Week 24
TRR2 is defined as ≥50% reduction in transfused RBC volume (normalized by weight) from week 13 to week 24 compared with historical RBC transfusion volume (normalized by weight) and standardized to 12 weeks.
Time frame: Baseline, Week 13 through Week 24
Percentage of Participants Who Achieved TRR3 From Week 25 to Week 36
TRR3 is defined as ≥50% reduction in transfused RBC volume (normalized by weight) from week 25 to week 36 compared with historical RBC transfusion volume (Normalized by Weight) and standardized to 12 weeks.
Time frame: Baseline, Week 25 through Week 36
Percentage of Participants Who Achieved TRR4 From Week 37 to Week 48
TRR4 is defined as ≥50% reduction in transfused RBC volume (normalized by weight) from week 37 to week 48 compared with historical RBC transfusion volume (normalized by weight) and standardized to 12 weeks.
Time frame: Baseline, Week 37 through Week 48
Percentage of Participants Who Achieved TRR5 From Week 25 to Week 48
TRR5 is defined as ≥50% reduction in transfused RBC volume (normalized by weight) from week 25 to week 48 compared with historical RBC transfusion volume (normalized by weight) and standardized to 24 weeks.
Time frame: Baseline, Week 25 through Week 48
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Percent Change in Transfused RBC Volume (Normalized by Weight) From Week 13 Through Week 48 Compared With Historical Transfusion Volume (Normalized by Weight) and Standardized to 36 Weeks
Time frame: Baseline, Week 13 through Week 48
Percentage of Participants Who Achieved Transfused Independence Through Week 48
Transfusion independence is defined as transfusion-free for greater than or equal to 8 consecutive weeks through Week 48.
Time frame: Baseline, through Week 48
Change in the Number of Transfusion Episodes From Week 13 Through Week 48 Compared With Historical Number of Transfusion Episodes Standardized to 36 Weeks
Time frame: Baseline, Week 13 through Week 48
Change From Baseline in Serum Iron at Week 48
Time frame: Baseline, Week 48
Change From Baseline in Total Iron-Binding Capacity at Week 48
Time frame: Baseline, Week 48
Change From Baseline in Transferrin at Week 48
Time frame: Baseline, Week 48
Change From Baseline in Transferrin Saturation at Week 48
Time frame: Baseline, Week 48
Change From Baseline in Serum Ferritin Levels at Week 48
Time frame: Baseline, Week 48
Cohort 1: Change From Baseline in Estradiol Through Week 48
Time frame: Baseline, through Week 48
Cohort 1: Change From Baseline in Estrone Through Week 48
Time frame: Baseline, through Week 48
Cohort 1: Change From Baseline in Total Testosterone Through Week 48
Time frame: Baseline, through Week 48
Cohort 1: Change From Baseline in Free Testosterone Through Week 48
Time frame: Baseline, through Week 48
Cohort 1: Change From Baseline in Luteinizing Hormone Through Week 48
Time frame: Baseline, through Week 48
Cohort 1: Change From Baseline in Sexual Maturity Rating With Tanner Stage Through Week 48
Time frame: Baseline, through Week 48
Cohort 1: Percentage of Female Participants With Newly Developed Ovarian Cysts Through Week 48
Time frame: Baseline, through Week 48
Change From Baseline Over Time in Height-for-age Z-Score, Weight-for-age Z-Score, and Body Mass Index (BMI)-for-age Z-Score Through Week 48
Time frame: Baseline, through Week 48
Change from Baseline in Bone Mineral Density (BMD) Through Week 48
Time frame: Baseline, through Week 48
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study drug up to end of study (up to Week 196)
Plasma Concentration of Mitapivat
Time frame: Pre-dose, and at multiple timepoints (up to 7 hours post-dose) at Week 4
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Mitapivat
Time frame: Pre-dose, and at multiple timepoints (up to 7 hours post-dose) at Week 4
Maximum Observed Plasma Concentration (Cmax) of Mitapivat
Time frame: Pre-dose, and at multiple timepoints (up to 7 hours post-dose) at Week 4
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Mitapivat
Time frame: Pre-dose, and at multiple timepoints (up to 7 hours post-dose) at Week 4