Resolution of Sickle Cell Leg Ulcers With Voxelotor (RESOLVE)

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

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.

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease; Leg Ulcers
• Intervention / Treatment: Other: Placebo; Drug: Voxelotor Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403-000
    • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
  • Sao Paulo, Brazil, 01232-010
    • Esho Empresa De Servicos Hospitalares S.A/ Hospital Samaritano Higienopolis
  • São Paulo, Brazil, 01246-000
    • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
  • Bahia
    • Salvador, Bahia, Brazil, 41253-190
      • Hospital Sao Rafael
    • Salvador, Bahia, Brazil, 40110-060
      • Universidade Federal Da Bahia Hospital Universitário Professor Edgard Santos
    • Salvador, Bahia, Brazil, 40110-060
      • Complexo Hospitalar Universitário Professor Edgard Santos- Universidade Federal Da Bahia
  • MG
    • Belo Horizonte, MG, Brazil, 30130-100
      • Hospital das Clinicas da Universidade Federal de Minas Gerais
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-100
      • Hospital das Clinicas da Universidade Federal de Minas Gerais
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50070-460
      • Multihemo Servicos Medicos S/A
  • SP
    • Cerqueira Cesar - Sao Paulo, SP, Brazil, 05403-000
      • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
  • SÃO Paulo
    • Ribeirão Preto, SÃO Paulo, Brazil, 14051-140
      • Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo
• Kenya
  • Kisumu, Kenya, 40100
    • KEMRI Kondele Children's Hospital within Jaramogi Oginga Odinga Teaching and Referral Hospital.
  • Nairobi, Kenya, 00100
    • Gertrude's Children's Hospital
  • Nairobi, Kenya, 00200
    • Strathmore University Medical Centre
  • Nairobi, Kenya, 00100
    • KEMRI-Centre for Respiratory Diseases Research-Nairobi
  • Siaya, Kenya, 40600
    • KEMRI-CRDR, KEMRI Clinical Research Annex
  • Kakamega County
    • Butere, Kakamega County, Kenya, 50100
      • KEMRI Centre for Clinical Research Butere County Hospital
• Nigeria
  • Kaduna, Nigeria, 800212
    • Barau Dikko Teaching Hospital/Kaduna State University
  • Kano, Nigeria, 700233
    • Aminu Kano Teaching Hospital
  • Lagos, Nigeria, 100254
    • Lagos University Teaching Hospital
  • Abuja
    • Gwagwalada, Abuja, Nigeria, 902101
      • SYNLAB
  • Cross River
    • Calabar, Cross River, Nigeria, 540281
      • University of Calabar Teaching Hospital
  • FCT
    • Abuja, FCT, Nigeria, 902101
      • SYNLAB
    • Gwagwalada, FCT, Nigeria, 902101
      • University of Abuja Teaching Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Resolution of the Target Ulcers by Week 12 in 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.	Through Week 12 of randomized treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Resolution of Target Ulcers up to Week 12 in 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. 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.	From Day 1 to censoring date before Week 12 or maximum up to Week 12 of randomized treatment period, whichever occurred first
Change From Baseline in Total Surface Area of Target Ulcers at Week 12 in 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.	Baseline, Week 12 of randomized treatment period
Percentage of Participants With New Ulcers by Week 12 in 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.	Through Week 12 of randomized treatment period

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2022
• Primary Completion (Actual): June 26, 2024
• Study Completion (Actual): October 22, 2024

Study Registration Dates

• First Submitted: September 27, 2022
• First Submitted That Met QC Criteria: September 27, 2022
• First Posted (Actual): September 30, 2022

Study Record Updates

• Last Update Posted (Actual): July 9, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Sickle Cell Disease, SCD
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Hematologic Diseases; Skin Diseases; Skin Ulcer; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Ulcer; Leg Ulcer; Anemia, Sickle Cell
• Other Study ID Numbers: GBT440-042; C5341026 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No