Study to Evaluate the Effect of Voxelotor Administered Orally to Patients With Sickle Cell Disease (GBT_HOPE)

Study Overview
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Brief Summary
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A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of Voxelotor Administered Orally to Patients With Sickle Cell Disease

Detailed Description
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This is a randomized, placebo-controlled, double blind, parallel group, multicenter study of participants, age 12 to 65 years, with SCD. The key purpose for the study is to establish efficacy and safety of voxelotor as compared with placebo.

Official Title
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A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of Voxelotor Administered Orally to Patients With Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: voxelotor
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female study participants with sickle cell disease Participants have had at least 1 episode of vaso-occlusive crisis (VOC) in the past 12 months. Age 12 to 65 years Hemoglobin (Hb) ≥5.5 and ≤10.5 g/dL during screening For participants taking hydroxyurea (HU), the dose of HU (mg/kg) must be stable for at least 3 months prior to signing the ICF. Exclusion Criteria: More than 10 VOCs within the past 12 months that required a hospital, emergency room or clinic visit Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received a RBC transfusion for any reason within 60 days of signing the ICF Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF (i.e., a vaso-occlusive event cannot be within 14 days prior to signing the ICF) Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4 × upper limit of normal Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory) <30 mL/min/1.73 m^2 or on chronic dialysis

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dose 1<br>voxelotor | Drug: voxelotor<br> <br> * Other names: GBT440;|
| Active Comparator: Dose 2<br>voxelotor | Drug: voxelotor<br> <br> * Other names: GBT440;|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Increase in Hb >1 g/dL From Baseline to Week 24 | Number of participants with increase in Hb >1 g/dL from Baseline to Week 24 | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate | Number of Vaso-Occlusive Crisis (VOC) events averaged per year. | Baseline to Week 72 | 
| Percentage Change From Baseline in Hemolysis Measures | Percentage change from Baseline to week 24 in unconjugated bilirubin | Baseline to Week 24 | 
| Percentage Change From Baseline in Hemolysis Measures | Percentage change from Baseline to week 24 in the absolute reticulocyte which is used to estimate the degree of effective erythropoiesis. This values is important in Sickle Cell Disease and was reported by the central laboratory. | Baseline to Week 24 | 
| Percentage Change From Baseline in Hemolysis Measures | Percentage change from Baseline to week 24 in reticulocytes % which is a % of total Red Blood Cells (RBCs). | Baseline to Week 24 | 
| Percentage Change From Baseline in Hemolysis Measures | Percentage change from Baseline to week 24 in Lactate Dehydrogenase (LDH) | Baseline to Week 24 |