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: Active, not recruiting
• Conditions: Sickle Cell Disease; Leg Ulcers
• Intervention / Treatment: Other: Placebo; Drug: Voxelotor Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

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

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
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	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

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 (Estimated): June 26, 2024
• Study Completion (Estimated): August 20, 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): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Sickle Cell Disease, SCD
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Hematologic Diseases; Skin Ulcer; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Ulcer; Anemia, Sickle Cell; Leg Ulcer
• 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