A Phase 2 Open-label Study to Evaluate the Activity of Etavopivat on Transcranial Doppler Velocities in Pediatric Patients With Sickle Cell Disease Who Are at Increased Risk for Primary Stroke

Launched by FORMA THERAPEUTICS, INC. · Jul 12, 2023

Keywords

ClinConnect Summary

This clinical trial is investigating a new medication called etavopivat, aimed at helping children with sickle cell disease (SCD) who are at higher risk of having a stroke. The trial will involve children aged 12 to 16 years who have specific results from a test called transcranial Doppler (TCD) ultrasound. Participants will be divided into two groups based on their TCD results and whether they are currently taking a medication called hydroxyurea. Each participant will take etavopivat once a day for a year and will have regular visits to the clinic to monitor their health.

To be eligible for the study, children must have a confirmed diagnosis of sickle cell disease and specific TCD results indicating an increased risk for stroke. They should also have stable blood counts and meet other health criteria. Throughout the trial, participants will be closely monitored to ensure their safety and the effectiveness of etavopivat. If the study proves beneficial, there may be opportunities for continued treatment after the trial ends.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Patient's parent, legal guardian, or legal representative has provided documented informed consent and patients have provided age-appropriate assent
• Age:
• • 2. 12 to 16 years of age (inclusive) at time of screening
• Type of Participant and Disease Characteristics:
• • 3. Confirmed diagnosis of SCD
• • • Documentation of any SCD genotype (e.g. HbSS, HbSβ0 -thalassemia) based on prior history of laboratory testing. Molecular genotyping is not required. SCD genotype may be determined from the results of Hb electrophoresis, high-performance liquid chromatography, or similar testing.
• • 4. TAMMV greater than or equal to (≥) 170 cm/s in the ICA and/or MCA during the Screening Period and confirmed on 2 occasions and without history of primary ischemic or hemorrhagic stroke, transient ischemic attack, or severe central nervous system (CNS) vasculopathy on magnetic resonance angiography (MRA). This includes patients with cTCD (170-199 centimeter per second \[cm/s\]) or aTCD (≥ 200 cm/s). Patients with aTCD cohort must have refused transfusion therapy.
• • 5. Hb ≥ 6 grams per deciliter (g/dL) and lesser than or equal to (≤) 9 g/dL at screening
• • 6. For participants with aTCD and cTCD and already taking HU, the dose of HU milligram per kilogram (mg/kg) must be stable (no more than a 20% change in dosing except for weight-based changes) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments except for weight-based changes during the study, in the opinion of the Investigator.
• • Sex and Contraceptive Requirements
• • 7. Patients, who if female and of childbearing potential, are using acceptable methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and who if male, are willing to use acceptable methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug
• Exclusion Criteria:
• • Medical Conditions
• • 1. Female who is breast feeding or pregnant
• • 2. History of seizure disorder
• • 3. Prior overt stroke (a focal neurological deficit of acute onset) by history or significant concerns for history of overt stroke based on Screening MRL, history of transient ischemic attack, focal neurological deficit on standardized neurological examination, or concern for moderate or severe neurological deficit (which could be due to stroke) based on a positive "10 questions" screening. Patients with significant or suggestive severe CNS vasculopathy (ie, moya moya) of Grade 4 or higher based on MRA read locally.
• • 4. Significant cytopenias (absolute neutrophil count \[ANC\] \< 1.5 × 10\^3/microliter (µL), platelets \< 150,000/µL, reticulocytes \< 80,000/µL)
• • 5. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the local laboratory \< 30 mL/min/1.73 m\^2) or on chronic dialysis
• • 6. Hepatic dysfunction characterized by alanine aminotransferase (ALT) \> 4 × upper limit of normal (ULN) and/or direct bilirubin \> 3 × ULN
• 7. Patients with clinically significant bacterial, fungal, parasitic, or viral infection requiring systemic therapy or history of such infections leading to significant neurological impairment:
• • Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay screening/enrollment until active therapy has been completed.
• • Patients with acute viral infections (eg, coronavirus disease 2019 \[COVID-19\]) should delay screening/enrollment until the acute infection has resolved.
• • Patients enrolled in areas where malaria is prevalent must be on malaria prophylaxis based on regional guidance and resistance results. Note: Infection prophylaxis is allowed (see concomitant medication restrictions).
• • 8. Known human immunodeficiency virus (HIV) positivity
• • 9. Known infection with hepatitis B virus (hepatitis B surface antigen \[HepBsAg\] and hepatitis B core antibody \[HepBcAb\] positive.