Study to Evaluate the Effect of GBT440 on TCD in Pediatrics With Sickle Cell Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Voxelotor (GBT440) in Pediatric Participants With Sickle Cell Disease (HOPE Kids 2)

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Voxelotor
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants with Sickle Cell Anemia (SCA) HbSS, HbSβ0 thalassemia genotype TCD time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow ≥ 170 to 200cm/sec during the Screening Period Hb ≥ 5.5 and ≤ 10.5 g/dL during screening For participants taking HU, the dose of HU (mg/kg) must be stable for at least 90 days prior to signing the informed consent form (ICF) and/or assent form, and with no anticipated need for dose adjustments (other than weight based) or for initiation of HU for non-chronic use during the study, in the opinion of the Investigator Written informed parental/guardian consent and participant assent (where applicable) has been obtained per IRB/EC policy and requirements, consistent with ICH guidelines. Exclusion Criteria: Body weight < 10kg at the screening visit Hospitalization for VOC or acute chest syndrome (ACS) within the 14 days prior to execution of informed consent/assent More than 10 VOCs within the past 12 months that required hospitalization, emergency room, or clinic visit Stroke resulting in focal neurological deficit; previous silent infarcts are permitted. Known history or findings suggestive of significant cerebral vasculopathy History of seizure disorder Has been treated with erythropoietin or other hematopoietic growth factors within 28 days of signing informed consent/assent or if, in the opinion of the Investigator, there is an anticipated need for such agents during the study RBC transfusion therapy (also termed chronic, prophylactic, or preventative transfusion) or has received an RBC transfusion or exchange transfusion for any reason within 90 days of signing the informed consent/assent

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Voxelotor<br>Voxelotor 1500mg or equivalent daily as a tablet, dispersible tablet, or as powder for oral suspension. | Drug: Voxelotor<br>* Participants are randomized 1:1 to receive voxelotor or placebo.<br>|
| Placebo Comparator: Placebo<br>Matching placebo. | Drug: Placebo<br>* Matching placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TCD Measurement | The change in time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow, as measured by TCD. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TCD Flow Velocity |  | 48 and 96 weeks | 
| Time to Conversion to Abnormal TCD Flow Velocity | Time to conversion to abnormal TCD flow velocity (≥ 200 cm/sec) | 24, 48, and 96 weeks | 
| Time to Reversion to Normal TCD Flow Velocity | Time to reversion to normal TCD flow velocity (<170 cm/sec) | 24, 48, and 96 weeks | 
| TCD Flow Velocity Reduction | Proportion of participants with TCD flow velocity reduction ≥ 15 cm/sec | 24, 48, and 96 weeks | 
| Number of Participants with Change in Hemoglobin (Hb) from baseline |  | baseline, 24, 48, and 96 weeks | 
| Change in Unconjugated Bilirubin from baseline |  | baseline, 24, 48 and 96 weeks | 
| Change in Percent of Reticulocyte from baseline |  | baseline, 24, 48, and 96 weeks | 
| Change in Absolute Reticulocyte from baseline |  | baseline, 24, 48, and 96 weeks | 
| Change in Lactate Dehydrogenase (LDH) from baseline |  | baseline, 24, 48, and 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, Transcranial Doppler Ultrasound (TCD)