Trial Outcomes & Findings for Study to Assess the Safety and Efficacy of Brincidofovir in Treatment of Early Versus Late Adenovirus Infection (NCT NCT02087306)

NCT ID: NCT02087306

Last Updated: 2021-08-13

Results Overview

The primary efficacy endpoint was the evaluation of the effect of brincidofovir (BCV) on all-cause mortality when used for the treatment of disseminated adenovirus (AdV) disease in all hematopoietic cell transplant (HCT) recipients. The primary endpoint associated with this objective was all-cause mortality through Day 60.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

201 participants

Primary outcome timeframe

60 days

Results posted on

2021-08-13

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort A Allogeneic hematopoietic cell transplant recipients at risk of progression to disseminated adenovirus (AdV) disease (i.e., subjects with either asymptomatic AdV infection or localized adenovirus disease) and who weighed ≤120 kg. Subjects who weighed \<50 kg received 2 mg/kg (not-to-exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received BCV 100 mg twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).	Cohort B Allogeneic hematopoietic cell transplant recipients with disseminated adenovirus disease who weigh ≤120 kg. Subjects who weighed \<50 kg received 2 mg/kg brincidofovir (BCV; not to exceed 100 mg) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100 mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).	Cohort C Allogeneic hematopoietic cell transplant recipients who weighed \>120 kg and all other immunocompromised subjects with disseminated adenovirus (AdV) disease or subjects who were at risk of progression to disseminated AdV disease, as well as non-immunocompromised subjects with disseminated AdV disease. Subjects who weighed \<50 kg received 2 mg/kg (not to exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).
Overall Study STARTED	65	93	43
Overall Study COMPLETED	29	29	16
Overall Study NOT COMPLETED	36	64	27

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Assess the Safety and Efficacy of Brincidofovir in Treatment of Early Versus Late Adenovirus Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A n=65 Participants Allogeneic hematopoietic cell transplant recipients at risk of progression to disseminated adenovirus (AdV) disease (i.e., subjects with either asymptomatic AdV infection or localized adenovirus disease) and who weighed ≤120 kg. Subjects who weighed \<50 kg received 2 mg/kg (not-to-exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received BCV 100 mg twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).	Cohort B n=93 Participants Allogeneic hematopoietic cell transplant recipients with disseminated adenovirus disease who weigh ≤120 kg. Subjects who weighed \<50 kg received 2 mg/kg brincidofovir (BCV; not to exceed 100 mg) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100 mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).	Cohort C n=43 Participants Allogeneic hematopoietic cell transplant recipients who weighed \>120 kg and all other immunocompromised subjects with disseminated adenovirus (AdV) disease or subjects who were at risk of progression to disseminated AdV disease, as well as non-immunocompromised subjects with disseminated AdV disease. Subjects who weighed \<50 kg received 2 mg/kg (not to exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).	Total n=201 Participants Total of all reporting groups
Age, Continuous	19 years STANDARD_DEVIATION 17.4 • n=5 Participants	20 years STANDARD_DEVIATION 23.1 • n=7 Participants	17 years STANDARD_DEVIATION 21.9 • n=5 Participants	19 years STANDARD_DEVIATION 21.1 • n=4 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	30 Participants n=7 Participants	16 Participants n=5 Participants	72 Participants n=4 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	63 Participants n=7 Participants	27 Participants n=5 Participants	129 Participants n=4 Participants

PRIMARY outcome

Timeframe: 60 days

Outcome measures

Outcome measures
Measure	Cohort A n=65 Participants Allogeneic hematopoietic cell transplant recipients at risk of progression to disseminated adenovirus (AdV) disease (i.e., subjects with either asymptomatic AdV infection or localized adenovirus disease) and who weighed ≤120 kg. Subjects who weighed \<50 kg received 2 mg/kg (not-to-exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received BCV 100 mg twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).	Cohort B n=93 Participants Allogeneic hematopoietic cell transplant recipients with disseminated adenovirus disease who weigh ≤120 kg. Subjects who weighed \<50 kg received 2 mg/kg brincidofovir (BCV; not to exceed 100 mg) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100 mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).	Cohort C n=43 Participants Allogeneic hematopoietic cell transplant recipients who weighed \>120 kg and all other immunocompromised subjects with disseminated adenovirus (AdV) disease or subjects who were at risk of progression to disseminated AdV disease, as well as non-immunocompromised subjects with disseminated AdV disease. Subjects who weighed \<50 kg received 2 mg/kg (not to exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).
Number of Participants With All-Cause Mortality	9 Participants	27 Participants	8 Participants

SECONDARY outcome

Timeframe: Assessed 13 weeks (through 7 days post-last BCV dose); during treatment up to 12 weeks reported

Population: Subjects with AdV viremia at baseline in the Intention-to-Treat Analysis Set. The Intention-to-Treat Analysis Set included all subjects who received at least 1 dose of BCV.

A secondary endpoint was the evaluation of virologic response (plasma adenovirus \[AdV\] DNA viremia) to brincidofovir treatment. Blood (plasma) was collected at screening, before dosing on Day 1 (to establish baseline), and at each subsequent assessment during the treatment and post-treatment phases for the analysis of AdV DNA viremia. All samples collected for analysis of AdV were analyzed by the designated central virology laboratory using proprietary real-time quantitative polymerase chain reaction (qPCR) assays. AdV in plasma were analyzed using the 7500 AdV qPCR Test, where the standardized assay plasma ranged from 190 copies/mL to 1 X 10\^10 copies/mL. A "positive or detectable" result referred to the measurement of AdV DNA at concentrations ≥190 copies/mL, a result below the lower limit of detection (LLOQ) (i.e., not detected) was imputed as 1 copy/mL, and a result below the lower limit of quantitation but detected will be imputed at 1 unit less than LLOQ (e.g., 189 copies/mL).

Outcome measures

Outcome measures
Measure	Cohort A n=41 Participants Allogeneic hematopoietic cell transplant recipients at risk of progression to disseminated adenovirus (AdV) disease (i.e., subjects with either asymptomatic AdV infection or localized adenovirus disease) and who weighed ≤120 kg. Subjects who weighed \<50 kg received 2 mg/kg (not-to-exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received BCV 100 mg twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).	Cohort B n=86 Participants Allogeneic hematopoietic cell transplant recipients with disseminated adenovirus disease who weigh ≤120 kg. Subjects who weighed \<50 kg received 2 mg/kg brincidofovir (BCV; not to exceed 100 mg) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100 mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).	Cohort C n=30 Participants Allogeneic hematopoietic cell transplant recipients who weighed \>120 kg and all other immunocompromised subjects with disseminated adenovirus (AdV) disease or subjects who were at risk of progression to disseminated AdV disease, as well as non-immunocompromised subjects with disseminated AdV disease. Subjects who weighed \<50 kg received 2 mg/kg (not to exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).
Number of Participants With Reduction in Adenovirus Viremia Undetectable AdV viremia at any time on-treatment	30 Participants	52 Participants	17 Participants
Number of Participants With Reduction in Adenovirus Viremia Undetectable AdV viremia at last on-treatment value	25 Participants	41 Participants	16 Participants

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Subjects who had adenovirus viremia at baseline.

Outcome measures

Outcome measures
Measure	Cohort A n=41 Participants Allogeneic hematopoietic cell transplant recipients at risk of progression to disseminated adenovirus (AdV) disease (i.e., subjects with either asymptomatic AdV infection or localized adenovirus disease) and who weighed ≤120 kg. Subjects who weighed \<50 kg received 2 mg/kg (not-to-exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received BCV 100 mg twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).	Cohort B n=86 Participants Allogeneic hematopoietic cell transplant recipients with disseminated adenovirus disease who weigh ≤120 kg. Subjects who weighed \<50 kg received 2 mg/kg brincidofovir (BCV; not to exceed 100 mg) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100 mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).	Cohort C n=29 Participants Allogeneic hematopoietic cell transplant recipients who weighed \>120 kg and all other immunocompromised subjects with disseminated adenovirus (AdV) disease or subjects who were at risk of progression to disseminated AdV disease, as well as non-immunocompromised subjects with disseminated AdV disease. Subjects who weighed \<50 kg received 2 mg/kg (not to exceed 100 mg) brincidofovir (BCV) twice weekly, administered orally as the appropriate volume of 10-mg/mL liquid suspension. Subjects who weighed ≥50 kg received 100 mg BCV twice weekly, administered orally as one 100-mg tablet (or the appropriate volume of 10-mg/mL liquid suspension if unable to swallow solid medicine).
Mean Minimum On-treatment Value log10 Copies/mL Change From Baseline Minimum on-treatment value log10 copies/mL change from baseline	-2.67 log10 copies/mL Standard Deviation 1.559	-3.27 log10 copies/mL Standard Deviation 2.163	-3.11 log10 copies/mL Standard Deviation 2.127
Mean Minimum On-treatment Value log10 Copies/mL Change From Baseline Last on-treatment value log10 copies/mL change from baseline	-2.06 log10 copies/mL Standard Deviation 1.898	-2.61 log10 copies/mL Standard Deviation 2.338	-2.87 log10 copies/mL Standard Deviation 2.291

Adverse Events

Pediatric

Serious events: 93 serious events

Other events: 127 other events

Deaths: 0 deaths

Adult

Serious events: 58 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Chimerix, Inc.

Phone: 919-806-1074

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Within 12 months after the end of the Study at all sites, if no publication of the overall multi-center results has been made, institutions are entitled to publish their locally obtained results, provided the Sponsor is given opportunity to review and comment. Institution publications may be delayed up to an additional 60 days to allow Sponsor to seek patent protection.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Pediatric n=130 participants at risk Subjects aged 2 months to \<18 years.	Adult n=71 participants at risk Subjects aged ≥18 years
Infections and infestations Septic shock	6.2% 8/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	32.4% 23/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Adenovirus infection	2.3% 3/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	7.0% 5/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Staphylococcal bacteraemia	4.6% 6/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations BK virus infection	1.5% 2/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	4.2% 3/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Device-related infection	3.1% 4/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Pneumonia	1.5% 2/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	2.8% 2/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Sepsis	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	4.2% 3/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Clostridium difficile colitis	1.5% 2/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Escherichia baceraemia	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	2.8% 2/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Klebsiella sepsis	2.3% 3/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Rhinovirus infection	2.3% 3/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Staphylococcal infection	2.3% 3/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Candida infection	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Cystitis viral	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Cytomegalovirus viraemia	0.00% 0/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	2.8% 2/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Enterococcal bacteraemia	1.5% 2/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Enterovirus infection	1.5% 2/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Fungal infection	1.5% 2/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Klebsiella bacteraemia	1.5% 2/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Klebsiella infection	1.5% 2/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Otitis media acute	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Pneumonia adenoviral	0.00% 0/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	2.8% 2/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Pseudomonas infection	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Viral haemorrhagic cystitis	0.00% 0/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	2.8% 2/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Zygomycosis	1.5% 2/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Acinetobacter infection	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Acute sinusitis	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Adenoviral hepatitis	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Bacillus bacteraemia	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Bacterial infection	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Bronchopulmonary aspergillosis	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Candida pneumonia	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Candida sepsis	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Cerebral toxoplasmosis	0.00% 0/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Clostridium bacteraemia	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Clostridium difficile infection	0.00% 0/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Cronobacter infection	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Cystitis klebsiella	0.00% 0/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Cytomegalovirus infection	0.00% 0/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Enteroabacter bacteraemia	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.

Other adverse events
Measure	Pediatric n=130 participants at risk Subjects aged 2 months to \<18 years.	Adult n=71 participants at risk Subjects aged ≥18 years
Gastrointestinal disorders Diarrhoea	44.6% 58/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	36.6% 26/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Gastrointestinal disorders Vomiting	20.8% 27/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	28.2% 20/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Gastrointestinal disorders Abdominal pain	15.4% 20/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	32.4% 23/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Gastrointestinal disorders Nausea	7.7% 10/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	25.4% 18/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Gastrointestinal disorders Abdominal distension	6.2% 8/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	15.5% 11/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Gastrointestinal disorders Constipation	10.0% 13/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	7.0% 5/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Gastrointestinal disorders Gastrointestinal haemorrhage	6.9% 9/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	4.2% 3/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Gastrointestinal disorders Abdominal pain upper	2.3% 3/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	5.6% 4/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Gastrointestinal disorders Colitis	5.4% 7/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Gastrointestinal disorders Dyspepsia	2.3% 3/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	5.6% 4/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Candida infection	6.2% 8/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	9.9% 7/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations BK virus infection	6.2% 8/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	8.5% 6/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Clostridium difficile colitis	6.9% 9/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	4.2% 3/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Staphylococcal bacteraemia	8.5% 11/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Pneumonia	3.8% 5/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	8.5% 6/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Rhinovirus infection	7.7% 10/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Septic shock	6.2% 8/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	4.2% 3/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Infections and infestations Adenovirus infection	2.3% 3/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	7.0% 5/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Alanine aminotransferase increased	19.2% 25/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	11.3% 8/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Aspartate aminotransferase increased	17.7% 23/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	11.3% 8/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Blood bilirubin increased	17.7% 23/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	7.0% 5/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Blood potassium decreased	15.4% 20/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	8.5% 6/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Blood glucose increased	10.8% 14/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	11.3% 8/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Blood magnesium decreased	14.6% 19/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	2.8% 2/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Transaminases increased	6.2% 8/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	8.5% 6/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Blood albumin decreased	8.5% 11/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	1.4% 1/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Blood sodium increased	6.9% 9/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	4.2% 3/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Blood sodium decreased	6.9% 9/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	2.8% 2/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Blood calcium decreased	7.7% 10/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	0.00% 0/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Blood potassium increased	5.4% 7/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	4.2% 3/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Gamma-glutamyltranferase increased	5.4% 7/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	2.8% 2/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Weight decreased	3.8% 5/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	5.6% 4/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Investigations Blood alkaline phosphatase increased	1.5% 2/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	7.0% 5/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
General disorders Pyrexia	36.9% 48/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	22.5% 16/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
General disorders Fatigue	3.8% 5/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	19.7% 14/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
General disorders Multi-organ failure	9.2% 12/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	7.0% 5/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
General disorders Oedema peripheral	3.8% 5/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	11.3% 8/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
General disorders Asthenia	0.77% 1/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	5.6% 4/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Respiratory, thoracic and mediastinal disorders Respiratory failure	13.1% 17/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	7.0% 5/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.
Respiratory, thoracic and mediastinal disorders Cough	6.9% 9/130 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.	11.3% 8/71 • Adverse events that started on or after the first dose of BCV up to 7 days after the last dose of BCV (through 13 weeks) are reported. As specified in the Statistical Analysis Plan, adverse events were reported by age group (i.e., pediatric and adult) rather than by cohort to provide a more useful safety assessment. Differentiating pediatric from adult safety in this broad population was more useful than differentiating safety by cohort in this uncontrolled setting.