This study is a Phase 3, randomized, double-blind, placebo-controlled study of voxelotor in pediatric participants, aged ≥ 2 to \< 15 years old, with Sickle Cell Disease. The primary objective is to evaluate the effect of voxelotor on the TCD (Transcranial Doppler Ultrasound) measurements in SCD participants in this age range.
This study is a Phase 3, randomized, double-blind, placebo-controlled study of voxelotor in pediatric participants, aged ≥ 2 to \< 15 years old, with Sickle Cell Disease. The study will be conducted at approximately 50 international clinical sites, and will enroll approximately 224 participants. Participants will be randomized in a 1:1 ratio to receive voxelotor or placebo. All participants younger than 12 years of age and randomized to voxelotor will receive a dose based on their body weight, to provide exposure corresponding to the adult dose of 1500 mg/day.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
236
Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at Week 24
TAMMV is an ultrasound measurement used in transcranial Doppler (TCD) to assess blood flow in cerebral arteries. TCD flow velocities were categorized as follows: (i) Normal: \< 170 centimeter per second (cm/sec); (ii) Conditional: 170 to \< 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: \>= 200 cm/sec.
Time frame: Baseline (value at screening), Week 24
Change From Baseline in TAMMV Arterial Cerebral Blood Flow at Week 48
TAMMV is an ultrasound measurement used in TCD to assess blood flow in cerebral arteries. TCD flow velocities were categorized as follows: (i) Normal: \< 170 cm/sec; (ii) Conditional: 170 to \< 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: \>= 200 cm/sec.
Time frame: Baseline (value at Screening), Weeks 48
Time to Conversion to Abnormal TCD Flow
Time to conversion was the number of weeks from the date of randomization to the date of first determined TCD assessment when an abnormal TCD flow velocity (\>= 200 cm/sec) was determined. TCD flow velocities were categorized as follows: (i) Normal: \< 170 cm/sec; (ii) Conditional: 170 to \< 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: \>= 200 cm/sec. The stratified Log Rank Test was stratified by stratification factors: baseline HU use (yes; no), age group (2 to \<= 8 years; \>8 to \<15 years), and baseline TAMMV value (170 cm/sec to \< 185 cm/sec; 185 cm/sec to \< 200 cm/sec).
Time frame: Up to 96 weeks
Time to Reversion to Normal TCD Flow
TCD was used to assess cerebral artery blood flow velocity in children with sickle cell disease (SCD). Time to first normal TCD flow was the number of weeks from randomization to the date of first determined normal TCD flow. Normal is \< 170 cm/sec.
Time frame: Up to 96 weeks
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Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Miami
Miami, Florida, United States
Children's Healthcare of Atlanta: Hughes Spalding
Atlanta, Georgia, United States
Boston Children's Hospital - Clinical Research Pharmacy
Boston, Massachusetts, United States
Boston Children's Hospital
Boston, Massachusetts, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Medical University of South Carolina: Investigational Drug Services
Charleston, South Carolina, United States
Medical University of South Carolina: Shawn Jenkins Women's and Children's Hospital
Charleston, South Carolina, United States
Medical University of South Carolina
Charleston, South Carolina, United States
...and 25 more locations
Percentage of Participants With TAMMV Reduced by >=15 cm/Sec From Baseline at Weeks 24, 48 and 96
In this outcome measure, percentage of participants whose TAMMV reduced by \>=15 cm/sec from Baseline at Weeks 24, 48 and 96 is reported. TAMMV is an ultrasound measurement used in TCD to assess blood flow in cerebral arteries. TCD flow velocities are categorized as follows: (i) Normal: \< 170 cm/sec; (ii) Conditional: 170 to \< 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: \>= 200 cm/sec.
Time frame: At Weeks 24, 48 and 96
Change From Baseline in Hemoglobin (Hb) at Weeks 24, 48 and 96
Change from baseline in hemoglobin at weeks 24, 48 and 96 were reported in this outcome measure.
Time frame: Baseline (value at Screening), Weeks 24, 48 and 96
Percent Change From Baseline in Unconjugated Bilirubin at Weeks 24, 48 and 96
Percent change from baseline in unconjugated bilirubin at weeks 24, 48 and 96 was reported in this outcome measure.
Time frame: Baseline (value at Screening), Weeks 24, 48 and 96
Percent Change From Baseline in Reticulocyte at Weeks 24, 48 and 96
Percent change from baseline in reticulocyte at weeks 24, 48 and 96 was reported in this outcome measure.
Time frame: Baseline (value at Screening), Weeks 24, 48 and 96
Percent Change From Baseline in Absolute Reticulocyte at Weeks 24, 48 and 96
Percent change from baseline in absolute reticulocyte at weeks 24, 48 and 96 was reported in this outcome measure.
Time frame: Baseline (value at Screening), Weeks 24, 48 and 96
Percent Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 24, 48 and 96
Percent change from baseline in LDH at weeks 24, 48 and 96 was reported in this outcome measure.
Time frame: Baseline (value at Screening), Weeks 24, 48 and 96
Annualized Incidence Rate of Vaso-Occlusive Crises (VOCs)
VOC was defined as a composite of acute painful crisis and/or acute chest syndrome (ACS). Annualized incidence rate was defined as total number of events per total person-years on treatment. Total person-years was the sum of participants treatment period in years, which included the time from randomization date to the earliest of (last dose date, post-randomization HU initiation for participants with no HU at baseline, end of study, or study termination). The 95% CI of rate displayed the exact Poisson confidence limits.
Time frame: From randomization to the last dose date, post-randomization HU initiation with no HU at baseline, end of study or study termination, whichever occurred earlier (maximum up to 110 weeks)