ABSTRACT
P168 Table 1Overall safety showing proportion of participants with AEsParticipants, n (%) Cohort 1n=12 Cohort 2n=12 Cohort 3n=12 Cohort 4n=12 Cohort 8n=5 TotalN=53 Any AE 11 (92) 7 (58) 9 (75) 7 (58) 4 (80) 38 (72) Grade ≥3 AE 6 (50) 2 (17) 1 (8) 4 (33) 2 (40) 15 (28) SAE 5 (42) 2 (17) 0 3 (25) 1 (20) 11 (21) Treatment discontinuation due to AE 2 (17) 0 0 0 0 2 (4) Treatment-emergent death 1 (8) 1 (8) 0 0 1 (20) 3 (6) Grade 3–4 laboratory abnormalities 9 (75) 2 (17) 4 (33) 4 (36) 3 (60) 22 (42) ConclusionsRDV was generally well tolerated in children hospitalised for COVID-19 who were 28 days and older, weighing at least 3 kg. No new safety trends for RDV were identified and a high proportion of participants had clinical improvement. CARAVAN is ongoing for enrolment of full term and preterm neonates.
ABSTRACT
Background: Remdesivir (RDV) has been shown to shorten time to recovery in hospitalized adults with COVID-19. Some children who develop COVID-19 require hospitalization. Here we characterize the safety profile of RDV in 53 pediatric patients age 28 days to <18 years and describe clinical and virologic outcomes. Methods: CARAVAN (NCT04431453) is an ongoing open-label, single arm study of RDV in hospitalized patients <18 years with PCR-confirmed COVID-19. IV RDV was given for up to 10 days: 200mg on Day 1 followed by 100mg daily in Cohort 1 and 8 (<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 was assessed by adverse events (AEs) and lab tests (hematology, chemistry, urine, inflammatory, coagulation). Clinical outcomes included improvement on a 7-point ordinal scale, time to discharge, and oxygenation modality. Virologic outcomes included days to confirmed negative SARS-CoV-2 PCR (defined as 2 consecutive negative results). Results: At enrollment, median (IQR) age was 7y (2, 12) and weight was 24.6 (12.8, 55.1) Kg, 57% were female, 76% required supplemental oxygen, including 23% on invasive ventilation and 34% on high-flow oxygen (Table). Median number of RDV doses was 5 (4,8). Most patients (72%) experienced ≥1 AE;most common was constipation (17%). Serious AEs were reported for 21% of patients and none were study-drug related. Two patients with baseline transaminitis had non-serious AE of increased ALT contributing to premature discontinuation. Two patients died within the 30-day study period. Grade ≥ 3 lab abnormalities were reported in 42%;most common being decreased haemoglobin (n=9) and decreased eGFR levels (n=7). No safety trends related to RDV were apparent. In total, 85% showed clinical improvement on the 7-point ordinal scale by last assessment. Median (IQR) time to discharge was 8 (5, 17) days. By last assessment, 8% required supplemental oxygen, all of whom were invasively ventilated. Time to confirmed negative SARS-CoV-2 PCR CoV-2 PCR was 5 and 7 days from nasal/oropharyngeal samples in cohort 2 and 3, respectively, and not estimable in the other cohorts. Conclusion:RDV was safe and well tolerated among children 28 days to <18y treated for COVID-19. Overall, no safety trends for RDV were apparent and a high proportion, 85%, had clinical improvement. The study is ongoing with enrolment of full term and preterm neonates pending dose determination.
ABSTRACT
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.