Resolution of Sickle Cell Leg Ulcers With Voxelotor

Phase 3

Terminated

• Conditions: Sickle Cell Disease; Leg Ulcers
• Interventions: Drug: Voxelotor Oral Tablet; Other: Placebo

• Registration Number: NCT05561140
• Lead Sponsor: Pfizer

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-05-30
• Study First Submitted: 2022-09-27
• Study First Submitted QC: 2022-09-27
• Study First Posted: 2022-09-30
• Primary Completion: 2024-06-26
• Study Completion: 2024-10-22
• Status Verified: 2025-06
• Results First Submitted: 2025-06-24
• Results First Submitted QC: 2025-06-24
• Last Update Submitted: 2025-06-24
• Results First Posted: 2025-07-09
• Last Update Posted: 2025-07-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

1. Male or female participants with documented diagnosis of SCD (HbSS, HbS/β0 thalassemia)

2. Age 12 years and older

3. 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

4. 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

1. Target ulcer(s) healed by ≥ 25% during the standard of care run-in period prior to randomization
2. Active infection/purulence at ulcer site, or exposed tendon or bone at the ulcer site, based on Investigator's clinical judgment
3. Current osteomyelitis at or near the ulcer site
4. Known vascular abnormalities that would preclude healing in the opinion of the Investigator (eg, pre-existing severe arterial insufficiency in the affected limb)
5. Serum albumin < 2.0 g/dL
6. RBC transfusion within 60 days of initiation of study drug
7. Receiving regularly scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) during the study
8. Planned elective surgery within the next 6 months
9. Anemia due to bone marrow failure (eg, myelodysplasia)
10. Absolute reticulocyte count < 100 × 109/L
11. Screening alanine aminotransferase (ALT) > 4 × upper limit of normal (ULN)
12. Severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2 by Schwartz formula) or is on chronic dialysis
13. Clinically significant bacterial, fungal, parasitic, or viral infection that requires therapy

Other protocol-defined Eligibility Criteria that apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Voxeletor + SOC (Standard of Care)	Voxelotor Oral Tablet	-
Placebo + SOC (Standard of Care)	Placebo	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Resolution of the Target Ulcers by Week 12 in Randomized Treatment Period	Through Week 12 of randomized treatment period	An ulcer qualified as a target ulcer, if met the following criteria: a) duration of ulcer was greater than equal to (\>=) 2 weeks and less than (\<) 6 months at screening; b) healed by \<25 percent (%) during the SOC run-in phase prior to randomization; c) size was greater than (\>2) square centimeters (cm\^2) at any visit, prior to randomization. Resolution of the target ulcer was defined as skin re-epithelialization confirmed at 2 consecutive study visits, 2 weeks apart during the 12-week randomized treatment period. For participants with more than one target ulcer, all target ulcers must be confirmed resolved in order for the participant to be a responder.

Secondary Outcome Measures

Name	Time	Method
Time to Resolution of Target Ulcers up to Week 12 in Randomized Treatment Period	From Day 1 to censoring date before Week 12 or maximum up to Week 12 of randomized treatment period, whichever occurred first	An ulcer qualified as a target ulcer, if met the following criteria: a) duration of ulcer was \>=2 weeks and \<6 months at screening; b) healed by \<25% during the SOC run-in phase prior to randomization; c) size was \>2 cm\^2 at any visit, prior to randomization. Resolution of the target ulcer was defined as skin re-epithelialization confirmed at 2 consecutive study visits, 2 weeks apart during the 12-week randomized treatment period. Time to resolution of target ulcers was defined as the first time of the observed ulcer was resolved. For participants with more than one target ulcer, time to resolution of target ulcers was defined as time to the last target ulcer confirmed resolved. For participants who did not have the last target ulcer confirmed resolved by Week 12 or who were discontinued from study, the time to resolution was censored. Median time to event was evaluated using Kaplan-Meier method.
Change From Baseline in Total Surface Area of Target Ulcers at Week 12 in Randomized Treatment Period	Baseline, Week 12 of randomized treatment period	An ulcer qualified as a target ulcer, if met the following criteria: a) duration of ulcer was \>=2 weeks and \<6 months at screening; b) healed by \<25% during the SOC run-in phase prior to randomization; c) size was \>2 cm\^2 at any visit, prior to randomization.
Percentage of Participants With New Ulcers by Week 12 in Randomized Treatment Period	Through Week 12 of randomized treatment period	New ulcers were defined as ulcer(s) that were not captured at visit 1/screening. In this outcome measure, participants with occurrence of new ulcers during 12 weeks of treatment were considered.

Trial Locations

Locations (20)

University of Abuja Teaching Hospital; 🇳🇬 Gwagwalada, FCT, Nigeria

Complexo Hospitalar Universitário Professor Edgard Santos- Universidade Federal Da Bahia; 🇧🇷 Salvador, Bahia, Brazil

Universidade Federal Da Bahia Hospital Universitário Professor Edgard Santos; 🇧🇷 Salvador, Bahia, Brazil

Hospital São Rafael; 🇧🇷 Salvador, Bahia, Brazil

Hospital das Clinicas da Universidade Federal de Minas Gerais; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Multihemo Servicos Medicos S/A; 🇧🇷 Recife, Pernambuco, Brazil

Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo; 🇧🇷 São Paulo, Brazil

Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de Sao Paulo; 🇧🇷 Ribeirão Preto, SÃO Paulo, Brazil

Esho Empresa De Servicos Hospitalares S.A/ Hospital Samaritano Higienopolis; 🇧🇷 Sao Paulo, Brazil

KEMRI Centre for Clinical Research Butere County Hospital; 🇰🇪 Butere, Kakamega County, Kenya

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