Safety and efficacy of remdesivir in a pediatric covid-19 population

Background: COVID-19 is generally a mild disease in children and infants. However, a small proportion develop severe disease requiring intensive care and ventilatory support. Remdesivir (RDV), a direct-acting nucleotide pro-drug inhibitor of viral RNA-dependent RNA polymerases, has been shown to shorten time to recovery in adults with severe COVID-19. The aim of this study is to evaluate the safety and efficacy of RDV in pediatric patients. Methods: CARAVAN (NCT04431453) is an ongoing open-label study of RDV in hospitalized pediatric patients with PCR-confirmed COVID-19. IV RDV is given for up to 10 days: 200mg on Day 1 followed by 100mg daily in Cohort 1 (12 to <18y, weight ≥40kg) or 5mg/kg on Day 1 followed by 2.5mg/kg daily in Cohorts 2-4 (28 days to <18y, stratified by weight). Safety is assessed by adverse events (AEs) and laboratory tests. Efficacy assessments include change in oxygen requirements and clinical status on a 7-point ordinal scale through Day 10. Results: Preliminary results for the first 27 patients are presented. Median (range) age and weight were: Cohort 1, 15 (12-17)y and 84 (47-192)kg;Cohort 2, 8 (4-16)y and 27 (25-39)kg;Cohort 3, 3 (2-5)y and 16 (12-18)kg;Cohort 4, 6 (2-11)m and 7 (3-10)kg. Overall, 52% were <12y, 56% were female, and 96% had ≥1 comorbid medical condition. Median number of RDV doses was 5;most RDV discontinuations were due to clinical improvement. At baseline, 67% required supplemental oxygen, including 22% on invasive ventilation;at Day 10, the values were 26% and 15%, respectively. In total, 70% showed clinical improvement on the 7-point ordinal scale at Day 10. Most (78%) had ≥1 AE, including 17% with study drug-related AEs;7% discontinued study drug due to an AE. Serious AEs were reported for 33% of patients;no SAEs were study drug related. Two patients died within 30 days of completing treatment. Grade 3 or 4 lab abnormalities were reported in 52%;those reported in ≥1 patient were decreased hemoglobin (n=5), and hypoglycemia, glycosuria, and increased PTT (n=2 each). No safety trends related to RDV were apparent. Conclusion: Among pediatric patients aged 2m to 17y treated with RDV for COVID-19, 70% had clinical improvement. The study is ongoing;enrolment of full term and preterm neonates is pending determination of the dose to be evaluated.