Evaluating Etavopivat for Pediatric Sickle Cell Disease Patients at Risk for Stroke

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

This study is testing if a new medication called etavopivat can help prevent strokes in kids aged 12 to 16 with sickle cell disease who are at higher risk.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 12 Years to 16 Years
• Sex: All
• Sponsor: Novo Nordisk A/S (Industry-sponsored)
• Locations: 9 sites (Raipur, Chhattisgarh and 8 other locations)
• Trial ID: NCT05953584 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety and efficacy of etavopivat in pediatric patients aged 12 to 16 years with sickle cell disease who are at increased risk for stroke. Participants will be divided into two cohorts based on their transcranial doppler (TCD) ultrasound results and their use of hydroxyurea. The treatment will last for 52 weeks, during which participants will take 400 mg of etavopivat daily. The study will monitor changes in TCD velocities to evaluate the drug's effectiveness in reducing stroke risk.

Who should consider this trial

Good fit: Ideal candidates are pediatric patients aged 12 to 16 with a confirmed diagnosis of sickle cell disease and specific TCD results indicating increased stroke risk.

Not a fit: Patients with a history of primary ischemic or hemorrhagic stroke or severe CNS vasculopathy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of stroke in children with sickle cell disease.

How similar studies have performed: Other studies have explored treatments for sickle cell disease, but the specific use of etavopivat in this context is novel.

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.

Where this trial is running

Raipur, Chhattisgarh and 8 other locations

• All India Institute of Medical Sciences (AIIMS), Raipur — Raipur, Chhattisgarh, India (Recruiting)
• All India Institute of Medical Sciences-Delhi — Delhi, India (Recruiting)
• Nirmal Hospital Pvt. Ltd. — Gujarat, India (Recruiting)
• Suretech Hospital and Research Centre Ltd. — Maharashtra, India (Recruiting)
• Indira Gandhi Government Medical College & Hospital — Nagpur, India (Not_yet_recruiting)
• University of Ibadan, University College Hospital — Ibadan, Nigeria (Recruiting)
• Lagos University Teaching Hospital, Lagos — Lagos, Nigeria (Recruiting)
• Aminu Kano Teaching Hospital (AKTH) — Tarauni, Nigeria (Recruiting)
• Sultan Qaboos University Hospital — Muscat, Sultanet of Oman/Muscat/Al Khoud, Oman (Recruiting)

Study contacts

• Study coordinator: Novo Nordisk

Conditions Sickle Cell Disease