Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients with Sickle Cell Disease

Recruitment & Eligibility

Status: Pending

Sex: All

Target Recruitment: 8

Inclusion Criteria

Type of Participant and Disease Characteristics
1. Patient has confirmed diagnosis of SCD
• Documentation of SCD genotype (HbSS, HbSß0-thalassemia or other sickle cell syndrome variants) 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 (HPLC), or similar testing. Note that Hb electrophoresis is performed by the local laboratory at Screening.
2. Hemoglobin = 5.5 and < 10.5 g/dL
3. Adolescent patients with severe SCD, as defined by at least 1 of the following:
• Two or more VOCs in the past 12 months, defined as a previously documented episode of acute chest syndrome (ACS) or acute painful crisis (for which there was no explanation other than VOC) which required prescription or healthcare professional-instructed use of analgesics for moderate to severe pain
• Hospitalization for any SCD-related complication in the last 12 months
• Proteinuria, defined as an albumin:creatinine ratio (ACR) > 100 mg/g on 2 measures (separated by = 1 month) as an indicator of early renal disease
• History of a conditional TCD in the last 12 months, but not currently being treated with chronic transfusion therapy. Conditional TCD is defined as a TAMMV of 170-199 cm/s by TCD or 155-184 cm/s by imaging TCD (TCDi).
4. For participants taking HU, the dose of HU (mg/kg) must be stable (no more than a 20% change in dosing) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments during the study, in the opinion of the Investigator
5. Patients on crizanlizumab or L-glutamine treatment at the time of consent may be eligible if they:
• Have been on a stable dose for = 12 months at the time of consent (ie, no changes to the dose except for changes to weight or for safety reasons)
• For patients on crizanlizumab, have been = 80% compliant

Exclusion Criteria

Medical Conditions
1. More than 10 VOCs within the past 12 months that required a hospital, emergency room (ER), or clinic visit
2. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of Screening
3. Abnormal TCD in the prior 12 months
Prior/Concomitant Therapy
4. Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion)
5. Received any blood products within 30 days of starting study treatment
6. Receiving or use of concomitant medications that are strong inducers of cytochrome P450 (CYP) 3A4/5 within 2 weeks of starting study treatment
7. Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study
8. Receipt of erythropoietin or other hematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study
9. Receipt of prior cellular based therapy (eg, hematopoietic cell transplant, gene modification therapy)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
ame: To assess the PK of etavopivat in patients with SCD;Timepoints: -;Measure: Single-dose: maximum concentration (Cmax), area under the concentration time curve (AUC)0-t, AUC0-inf;Name: To assess the PK of etavopivat in patients with SCD;Timepoints: -;Measure: Steady-state etavopivat plasma exposure (Cmax,ss, AUCtau,ss, Cavg,ss, Cmin,ss);Name: To assess the PK of etavopivat in patients with SCD;Timepoints: -;Measure: Estimated using population PK;Name: To assess the safety and tolerability of etavopivat;Timepoints: During the 24-week primary treatment period;Measure: Incidence of adverse events (AEs), serious adverse events (SAEs), and AEs related to etavopivat;Name: To assess the safety and tolerability of etavopivat;Timepoints: During the 24-week primary treatment period;Measure: Number of premature discontinuations, dose interruptions, and dose reductions

Secondary Outcome Measures