Resolution of Sickle Cell Leg Ulcers With Voxelotor (RESOLVE)

Pfizer

Status and phase: Terminated; Phase 3

Conditions: Leg Ulcers; Sickle Cell Disease

Treatments: Other: Placebo; Drug: Voxelotor Oral Tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT05561140

C5341026 (Other Identifier)

GBT440-042

Details and patient eligibility

About

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.

Enrollment: 88 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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88 participants in 2 patient groups, including a placebo group

Voxeletor + SOC (Standard of Care)

Experimental group

Treatment:

Drug: Voxelotor Oral Tablet

Placebo + SOC (Standard of Care)

Placebo Comparator group

Treatment:

Other: Placebo