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: 2024-11
• Last Update Submitted: 2024-11-12
• Last Update Posted: 2024-11-14

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
The effect of voxelotor and standard of care compared to placebo and SOC on leg ulcer healing	From pre-dose to Week 12	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

Secondary Outcome Measures

Name	Time	Method
Change in total surface area(s) of target ulcer(s)	From pre-dose to Week 12
Time to resolution of target ulcer(s)	From pre-dose to Week 12
Incidence of new ulcers	From pre-dose to Week 12

Trial Locations

Locations (20)

KEMRI-Centre for Respiratory Diseases Research-Nairobi; 🇰🇪 Nairobi, Kenya

Strathmore University Medical Centre; 🇰🇪 Nairobi, Kenya

KEMRI-CRDR, KEMRI Clinical Research Annex; 🇰🇪 Siaya, Kenya

SYNLAB; 🇳🇬 Abuja, FCT, Nigeria

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

KEMRI Kondele Children's Hospital within Jaramogi Oginga Odinga Teaching and Referral Hospital.; 🇰🇪 Kisumu, Kenya

Gertrude's Children's Hospital; 🇰🇪 Nairobi, Kenya

University of Calabar Teaching Hospital; 🇳🇬 Calabar, Cross River, Nigeria

Barau Dikko Teaching Hospital/Kaduna State University; 🇳🇬 Kaduna, Nigeria

Aminu kano Teaching Hospital; 🇳🇬 Kano, Nigeria

Lagos University Teaching Hospital; 🇳🇬 Lagos, Nigeria