The primary objective of this study is to compare the effect of mitapivat versus placebo on anemia in pediatric participants with alpha- or beta-non-transfusion-dependent thalassemia.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
45
Tablets or Granules
Tablets or Granules
Percentage of Participants Who Achieved a Hemoglobin (Hb) Response
Hb response is defined as a ≥1.0 grams per deciliter (g/dL) increase in average Hb concentration from Week 12 through Week 24 compared with baseline.
Time frame: Baseline, Week 12 through Week 24
Change From Baseline in Average Hb Concentration From Week 12 Through Week 24
Time frame: Baseline, Week 12 through Week 24
Percentage of Participants Who Achieved a Hb 1.5+ Response
Hb 1.5+ response is defined as a ≥1.5 g/dL increase in average Hb concentration from Week 12 through Week 24 compared with Baseline.
Time frame: Baseline, Week 12 through Week 24
Change From Baseline in Indirect Bilirubin at Week 24
Time frame: Baseline, Week 24
Change From Baseline in Lactate Dehydrogenase (LDH) at Week 24
Time frame: Baseline, Week 24
Change From Baseline in Haptoglobin at Week 24
Time frame: Baseline, Week 24
Change From Baseline in Reticulocytes at Week 24
Time frame: Baseline, Week 24
Change From Baseline in Erythropoietin at Week 24
Time frame: Baseline, Week 24
Cohort 1: Change From Baseline in Estradiol Through Week 24
Time frame: Baseline, up to Week 24
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Cohort 1: Change From Baseline in Estrone Through Week 24
Time frame: Baseline, up to Week 24
Cohort 1: Change From Baseline in Total Testosterone Through Week 24
Time frame: Baseline, through Week 24
Cohort 1: Change From Baseline in Free Testosterone Through Week 24
Time frame: Baseline, through Week 24
Cohort 1: Change From Baseline in Luteinizing Hormone Through Week 24
Time frame: Baseline, through Week 24
Cohort 1: Change From Baseline in Sexual Maturity Rating With Tanner Stage Through Week 24
Time frame: Baseline, through Week 24
Cohort 1: Percentage of Female Participants With Newly Developed Ovarian Cysts Through Week 24
Time frame: Baseline, through Week 24
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 24
Time frame: Baseline, through Week 24
Change from Baseline in Bone Mineral Density (BMD) Through Week 24
Time frame: Baseline, through Week 24
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of the study drug to the end of DB period (through Week 24)
Change from Baseline Through Week 24 in Pediatric Quality of Life (PedsQL) Multidimensional Fatigue Scale
The PedsQL Multidimensional Fatigue Scale measures dimensions of fatigue over a 7-day recall period. It includes 3 subscales: general fatigue, sleep/rest fatigue, and cognitive fatigue. Items are reverse-scored and linearly transformed to a 0-100 scale so that higher PedsQL Multidimensional Fatigue Scale scores indicate better health-related quality of life (HRQOL) (fewer symptoms of fatigue).
Time frame: Baseline, through Week 24
Change from Baseline Through Week 24 in PedsQL 4.0 Generic Core Scale (GCS)
HRQOL will be assessed using the PedsQL Multidimensional 4.0 Generic Core Scales (for participants 2 years or older). The PedsQL 4.0 Generic Core Scales are multidimensional, well-validated measures of quality of life in childhood. They each consist of 4 subscales: physical health, emotional functioning, social functioning, and school functioning are reverse-scored and linearly transformed to a 0-100 scale, with higher scores indicating better HRQOL.
Time frame: Baseline, through Week 24
Change From Baseline in Serum Iron at Week 24
Time frame: Baseline, Week 24
Change From Baseline in Total Iron-binding Capacity at Week 24
Time frame: Baseline, Week 24
Change From Baseline in Transferrin at Week 24
Time frame: Baseline, Week 24
Change From Baseline in Transferrin Saturation at Week 24
Time frame: Baseline, Week 24
Change From Baseline in Serum Ferritin at Week 24
Time frame: Baseline, Week 24
Plasma Concentration of Mitapivat
Time frame: Pre-dose and at multiple timepoints post-dose (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 post-dose (up to 7 hours post-dose) at Week 4
Maximum Observed Plasma Concentration (Cmax) of Mitapivat
Time frame: Pre-dose and at multiple timepoints post-dose (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 post-dose (up to 7 hours post-dose) at Week 4