Resolution of Sickle Cell Leg Ulcers With Voxelotor

Study Overview
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Brief Summary
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This study is a Phase 3, multicenter, randomized, placebo-controlled study to evaluate the efficacy of voxelotor and standard of care for the treatment of leg ulcers in participants with sickle cell disease. The study is divided into a 5 study periods: Screening, Run-in, Randomized Treatment, Open-label Treatment, and Follow-up/End of Study (EOS). The study will be conducted in approximately 80 eligible participants at approximately 20 global clinical trial sites.

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy of Voxelotor for the Treatment of Leg Ulcers in Patients With Sickle Cell Disease

Conditions
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Sickle Cell Disease, Leg Ulcers

Intervention / Treatment
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* Drug: Voxelotor Oral Tablet
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants with documented diagnosis of SCD (HbSS, HbS/β0 thalassemia) Age 12 years and older At least 1 cutaneous ulcer(s) on the lower extremity (leg, ankle, or dorsum of foot) that meets the following criteria: Duration: ≥ 2 weeks and < 6 months at Screening, and Size: > 2 cm2 prior to randomization Written informed consent (≥ 18 years) or parental/guardian consent and participant assent (≥ 12-17 years) per IEC policy and requirements, consistent with ICH guidelines Exclusion Criteria: Target ulcer(s) healed by ≥ 25% during the standard of care run-in period prior to randomization Active infection/purulence at ulcer site, or exposed tendon or bone at the ulcer site, based on Investigator's clinical judgment Current osteomyelitis at or near the ulcer site Known vascular abnormalities that would preclude healing in the opinion of the Investigator (eg, pre-existing severe arterial insufficiency in the affected limb) Serum albumin < 2.0 g/dL RBC transfusion within 60 days of initiation of study drug Receiving regularly scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) during the study Planned elective surgery within the next 6 months Anemia due to bone marrow failure (eg, myelodysplasia) Absolute reticulocyte count < 100 × 109/L Screening alanine aminotransferase (ALT) > 4 × upper limit of normal (ULN) Severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2 by Schwartz formula) or is on chronic dialysis Clinically significant bacterial, fungal, parasitic, or viral infection that requires therapy Other protocol-defined Eligibility Criteria that apply

Ages Eligible for Study
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Minimum Age: 12 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Voxeletor + SOC (Standard of Care)<br> | Drug: Voxelotor Oral Tablet<br>* Synthetic small molecule supplied as 500 mg tablets, administered Orally<br>|
| Placebo Comparator: Placebo + SOC (Standard of Care)<br> | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of voxelotor and standard of care compared to placebo and SOC on leg ulcer healing | To assess the effect of voxelotor and standard of care compared to placebo and SOC on leg ulcer healing in participants ≥ 12 years of age with SCD, as measured by the proportion of participants with complete resolution of target ulcer(s) in each treatment group by Week 12 | From pre-dose to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to resolution of target ulcer(s) |  | From pre-dose to Week 12 | 
| Change in total surface area(s) of target ulcer(s) |  | From pre-dose to Week 12 | 
| Incidence of new ulcers |  | From pre-dose to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, SCD