A Study to Evaluate 5 μg/kg Tbo-filgrastim in Infants, Ch... | NCT02190721

ID	Type	Description	Link
2014-001772-55	EudraCT Number

Label	Type	Description	Intervention Names
tbo-filgrastim	Experimental	Patients will receive subcutaneous doses of tbo-filgrastim 5 μg/kg body weight daily; each daily dose, to be administered at the investigative site	Drug: tbo-filgrastim

Name	Type	Description	Arm Group Labels	Other Names
tbo-filgrastim	Drug	5 μg/kg	tbo-filgrastim

Measure	Description	Time Frame
Participants With Adverse Events (AEs)	An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. A treatment-emergent AE (TEAE) is an AE occurring during the timeframe. A non-TEAE is any AE not considered a TEAE. Severity was rated by the investigator using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale where 3=severe but not life-threatening, 4=life-threatening and 5=death. Relation of AE to treatment was determined by the investigator (related=reasonable possibility). Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.	Non-TEAE: signing of informed consent to Day -1 (last day of CTX in week 1). And > 30 days after last dose of tbo-filgrastim (Day 46+). TEAE timeframe: Day 1 (start of tbo-filgrastim) to <= 30 days after the last dose (up to Day 45)
Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results	Serum chemistry tests included alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin, indirect bilirubin, total bilirubin, calcium, creatinine, gammaglutamyl transpeptidase (GGT), glucose, potassium, lactate dehydrogenase (LDH), phosphate, sodium and uric acid. Only tests with potentially clinically significant abnormal results are reported. ULN = upper limit of normal	Day 1 (start of tbo-filgrastim administration) up to Day 21
Participants With Potentially Clinically Significant Abnormal Hematology Results	Hematology tests included Basophils ABS (x 10^9/L), Basophils (%), Eosinophils ABS (x 10^9/L), Eosinophils (%), Hematocrit (%), Hemoglobin (g/L), Lymphocytes Absolute Count (ABS) (x 10^9/L), Lymphocytes (%), Monocytes ABS (x 10^9/L), Monocytes (%), Neutrophils ABS (x 10^9/L), Neutrophils (%), Platelets (x 10^9/L), Red Blood Cell (RBC) (x 10^12/L), White Blood Cell (WBC) (x 10^9/L). Only tests with potentially clinically significant abnormal results are reported. ULN = upper limit of normal

Measure	Description	Time Frame
Participants With Positive Immunogenicity Findings Tested at Four Study Timepoints	Blood was drawn for the assessment of anti-drug antibody (ADA) at screening, at the end-of-study visit, and at 30 and 90 days after the last administration of tbo-filgrastim in chemotherapy (CTX) cycle 1. The main endpoint from the assessment was the presence of antibodies in the sample, reported as positive or negative. Participants with positive results are summarized.

Name	Affiliation	Role
Teva Medical Expert, MD	Teva Branded Pharmaceutical Products R&D, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Teva Investigational Site 12958		Long Beach	California	90806	United States
Teva Investigational Site 12951

ID	Title	Description
FG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 24, 2016	May 18, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Participants With Adverse Events (AEs)

An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. A treatment-emergent AE (TEAE) is an AE occurring during the timeframe. A non-TEAE is any AE not considered a TEAE.

Severity was rated by the investigator using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale where 3=severe but not life-threatening, 4=life-threatening and 5=death. Relation of AE to treatment was determined by the investigator (related=reasonable possibility). Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

Safety analysis set. The safety analysis set included all enrolled patients who received at least 1 dose of tbofilgrastim.

Posted

Count of Participants

Participants

Non-TEAE: signing of informed consent to Day -1 (last day of CTX in week 1). And > 30 days after last dose of tbo-filgrastim (Day 46+). TEAE timeframe: Day 1 (start of tbo-filgrastim) to <= 30 days after the last dose (up to Day 45)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG002	Adolescents (12 to <16 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Units	Counts
Participants	OG0002 OG00130 OG00218

Title

Denominators

Categories

Any adverse event

Title	Measurements
	OG0002 OG00128 OG00216

Any TEAE

Primary

Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results

Serum chemistry tests included alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin, indirect bilirubin, total bilirubin, calcium, creatinine, gammaglutamyl transpeptidase (GGT), glucose, potassium, lactate dehydrogenase (LDH), phosphate, sodium and uric acid.

Only tests with potentially clinically significant abnormal results are reported.

ULN = upper limit of normal

Safety analysis set

Posted

Count of Participants

Participants

Day 1 (start of tbo-filgrastim administration) up to Day 21

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Primary

Participants With Potentially Clinically Significant Abnormal Hematology Results

Hematology tests included Basophils ABS (x 10^9/L), Basophils (%), Eosinophils ABS (x 10^9/L), Eosinophils (%), Hematocrit (%), Hemoglobin (g/L), Lymphocytes Absolute Count (ABS) (x 10^9/L), Lymphocytes (%), Monocytes ABS (x 10^9/L), Monocytes (%), Neutrophils ABS (x 10^9/L), Neutrophils (%), Platelets (x 10^9/L), Red Blood Cell (RBC) (x 10^12/L), White Blood Cell (WBC) (x 10^9/L).

Only tests with potentially clinically significant abnormal results are reported.

ULN = upper limit of normal

Safety analysis set

Posted

Count of Participants

Participants

Day 1 (start of tbo-filgrastim administration) up to Day 21

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Primary

Participants With Potentially Clinically Significant Abnormal Vital Signs

Vital sign tests included Pulse Rate (bpm), Systolic BP (mmHg), Diastolic BP (mmHg), Respiratory Rate (bpm), and Temperature (°C).

Only tests with potentially clinically significant abnormal results are reported.

Safety analysis set

Posted

Count of Participants

Participants

Day 1 (start of tbo-filgrastim administration) up to Day 21

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Primary

Participants With Potentially Clinically Significant Abnormal Electrocardiogram Results

Triplicate 12-lead ECGs were conducted at screening, predose, 4 and 6 hours postdose on day 1 of tbo-filgrastim administration, and at the end-of-study visit. The ECGs were interpreted by both the investigator and a qualified physician at the central diagnostic center as normal, abnormal not clinically significant, or abnormal clinically significant. The following parameters were measured/derived for each ECG assessment: heart rate, PR interval, RR interval, QT interval, corrected QT interval according to Fridericia's formula (QTcF), corrected QT interval according to Bazett's formula (QTcB), QRS duration, and QRS axis.

The count of participants with potentially clinically significant ECG findings is reported.

Safety analysis set

Posted

Count of Participants

Participants

Day 1 (start of tbo-filgrastim administration) pre-dose, 4 hours post dose and 6 hours post dose; Day 21 (end of study visit)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001

Primary

Participants With Negative Shifts From Baseline to End of Study in Physical Exam Findings

Physical examination was performed at screening and at the end-of-study visit. The following body systems were marked as normal or abnormal and if abnormal, whether clinically significant: Head, ears, eyes, nose and throat (HEENT), chest and lungs, heart, abdomen, skin, lymph nodes and neurological.

Any physical examination finding that is judged by the investigator as a clinically significant change (worsening) compared with a baseline value were considered as an adverse event.

Counts of participants with a negative shift from baseline in any of the body systems (including shifts from normal to abnormal, not clinically significant) are presented.

Safety analysis set

Posted

Count of Participants

Participants

Baseline: Day -21, Day 21 (end of study visit)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)

Primary

Participants With Injection Site Reactions to Tbo-Filgrastim Administration

Using Local Tolerability Assessment Scale ranging from Pain severity 0 (Absent) to 3 (Spontaneously painful)

Safety analysis set

Posted

Count of Participants

Participants

Day 1 (start of tbo-filgrastim administration) up to Day 14

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Primary

Participants With Negative Shifts From Baseline to End of Study in Spleen Sonography Findings

The investigator assessed spleen sonography findings as normal, abnormal not clinically significant, or abnormal clinically significant.

Data representing counts of participants with a negative shift from baseline in spleen sonography findings (including shifts from normal to abnormal, not clinically significant) are presented.

Safety analysis set

Posted

Count of Participants

Participants

Baseline: Day -21, Day 21 (end of study visit)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Primary

Participants Who Were Alive at the 90 Day Follow-Up

Summary of participant survival at 90 day follow-up.

Safety analysis set

Posted

Count of Participants

Participants

90 days post end of study visit (111 days from start of tbo-filgrastim administration)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Participants With Positive Immunogenicity Findings Tested at Four Study Timepoints

Blood was drawn for the assessment of anti-drug antibody (ADA) at screening, at the end-of-study visit, and at 30 and 90 days after the last administration of tbo-filgrastim in chemotherapy (CTX) cycle 1.

The main endpoint from the assessment was the presence of antibodies in the sample, reported as positive or negative. Participants with positive results are summarized.

Safety analysis set

Posted

Count of Participants

Participants

Baseline (Day -21), Day 21 (end of study visit), Day 51 (30 Day follow-up) and Day 111 (90 Day follow-up)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Maximum Observed Serum Concentration (Cmax) of Tbo-Filgrastim

Pharmacokinetic (PK) analysis set

Posted

Mean

Standard Deviation

pg/mL

Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG002

Secondary

Time to Maximum Observed Serum Concentration (Tmax) of Tbo-Filgrastim

PK analysis set

Posted

Median

Full Range

Hours

Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG002

Secondary

Area Under The Serum Concentration-Time Curve From Time 0 To Time Of Last Quantifiable Concentration (AUClast)

PK analysis set

Posted

Mean

Standard Deviation

hr*pg/mL

Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Area Under The Serum Concentration-Time Curve From Time 0 To 12 Hours Postdose (AUC0-12)

PK analysis set. In 4 participants, serum concentrations of tbo-filgrastim were not obtained through 12 hours and as a result, AUC0-12 could not be calculated.

Posted

Mean

Standard Deviation

hr*pg/mL

Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

AUC From Time 0 to Infinity (AUC0-inf)

PK analysis set. The 12 hour sampling duration limited the ability to characterize the terminal elimination rate of tbo-filgrastim (λz ) and related parameters (t½, AUC0-∞,-∞ %AUCex, CL/F, and Vz/F) for more than half of patients enrolled, especially those with maximum serum concentrations being achieved >= 6 hours. This included both infants.

Posted

Mean

Standard Deviation

hr*pg/mL

Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Elimination Half-life (t1/2)

Posted

Mean

Standard Deviation

hours

Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Apparent Clearance (CL/F)

Posted

Mean

Standard Deviation

L/hour

Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose of Day 1

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Apparent Volume of Distribution During the Terminal Phase (Vz/F)

Posted

Mean

Standard Deviation

liters

Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Percentage of the AUC0-∞ That Is Due To the Extrapolation (%AUCext)

Posted

Mean

Standard Deviation

percent of AUC0-∞

Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Terminal Elimination Rate (Lambda-z)

Posted

Mean

Standard Deviation

1/hr

Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Participants With Severe Neutropenia

Count of participants who had an incidence of severe neutropenia, defined as any value of absolute neutrophil count (ANC) <0.5 * 10^9/L at any time.

The Full Analysis Set (FAS) included all patients in the ITT population who received at least 1 dose of tbo-filgrastim and had at least 1 post baseline efficacy assessment.

Posted

Count of Participants

Participants

ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Duration of Severe Neutropenia

The duration of severe neutropenia was derived by counting the number of days with absolute neutrophil count (ANC) values <0.5 * 10^9/L.

Full analysis set

Posted

Mean

Standard Deviation

days

ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Area Under The Serum Drug Concentration By Time Curve Of Absolute Neutrophil Count (AUC ANC)

Full analysis set

Posted

Mean

Standard Deviation

*10^9/L * days

ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Absolute Neutrophil Count (ANC) Nadir

ANC nadir (measured in 10^9/L) is the lowest ANC recorded.

Full analysis set

Posted

Mean

Standard Deviation

*10^9/L

ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Time to Absolute Neutrophil Count (ANC) Nadir From Beginning of Tbo-filgrastim Administration

Full analysis set

Posted

Mean

Standard Deviation

days

ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Time to Absolute Neutrophil Count (ANC) Nadir From Beginning of Chemotherapy

Full analysis set

Posted

Mean

Standard Deviation

days

ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Time to ANC Recovery To ≥1.0 * 10^9/L From ANC Nadir

Full analysis set

Posted

Mean

Standard Deviation

days

ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG002

Secondary

Time to ANC Recovery To ≥2.0 * 10^9/L From ANC Nadir

Full analysis set

Posted

Mean

Standard Deviation

days

ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG002

Secondary

Time to ANC Recovery To ≥1.0 * 10^9/L From Start of Tbo-filgrastim Administration

Full analysis set

Posted

Mean

Standard Deviation

days

ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Time to ANC Recovery To ≥2.0 * 10^9/L From Start of Tbo-filgrastim Administration

Full analysis set

Posted

Mean

Standard Deviation

days

ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Time to ANC Recovery To ≥1.0 * 10^9/L From Start of Chemotherapy

Full analysis set

Posted

Mean

Standard Deviation

days

ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Time to ANC Recovery To ≥2.0 * 10^9/L From Start of Chemotherapy

Full analysis set

Posted

Mean

Standard Deviation

days

ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Secondary

Participants With Febrile Neutropenia During the First Cycle of Chemotherapy

Febrile neutropenia was defined as an axillary or external ear temperature >38.3°C (100.94°F) or 2 consecutive readings >37.8°C (100.04°F) at least 2 hours apart and an ANC <0.5 * 10^9/L. The efficacy variable was evaluated for up to 21 days from the start of the first cycle of chemotherapy.

Full analysis set

Posted

Count of Participants

Participants

(relative to tbo-filgrastim therapy) Days -7 to Day 14

ID	Title	Description
OG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
OG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0015 events4 affected30 at risk EG0020 events0 affected18 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0016 events4 affected30 at risk EG0022 events2 affected18 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected30 at risk EG0020 events0 affected18 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected30 at risk EG0022 events2 affected18 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected30 at risk EG0020 events0 affected18 at risk
Alanine aminotransferase increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected30 at risk EG0021 events1 affected18 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected30 at risk EG0021 events1 affected18 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0021 events1 affected18 at risk
Hangnail	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected30 at risk EG0020 events0 affected18 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected2 at risk EG00120 events12 affected30 at risk EG0023 events3 affected18 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected2 at risk EG0015 events5 affected30 at risk EG0020 events0 affected18 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0002 events2 affected2 at risk EG00111 events6 affected30 at risk EG0023 events3 affected18 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0023 events1 affected18 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0006 events2 affected2 at risk EG00134 events16 affected30 at risk EG00216 events9 affected18 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0005 events2 affected2 at risk EG00116 events8 affected30 at risk EG0025 events4 affected18 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0021 events1 affected18 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0022 events1 affected18 at risk
Abdominal rigidity	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0021 events1 affected18 at risk
Colitis	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected2 at risk EG0011 events1 affected30 at risk EG0020 events0 affected18 at risk
Constipation	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0021 events1 affected18 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected30 at risk EG0022 events1 affected18 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected30 at risk EG0020 events0 affected18 at risk
Nausea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected30 at risk EG0022 events2 affected18 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected2 at risk EG0013 events3 affected30 at risk EG0022 events2 affected18 at risk
Vomiting	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0016 events5 affected30 at risk EG0026 events3 affected18 at risk
Hyperthermia	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0021 events1 affected18 at risk
Mucosal inflammation	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0013 events3 affected30 at risk EG0023 events3 affected18 at risk
Pyrexia	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected30 at risk EG00210 events2 affected18 at risk
Hypogammaglobulinaemia	Immune system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0026 events3 affected18 at risk
Cellulitis staphylococcal	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0021 events1 affected18 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected30 at risk EG0022 events1 affected18 at risk
Oral candidiasis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0021 events1 affected18 at risk
Alanine aminotransferase increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected30 at risk EG0020 events0 affected18 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected30 at risk EG0020 events0 affected18 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0021 events1 affected18 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected30 at risk EG0020 events0 affected18 at risk
Neutrophil count decreased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0013 events2 affected30 at risk EG0020 events0 affected18 at risk
White blood cell count decreased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0013 events2 affected30 at risk EG0020 events0 affected18 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected30 at risk EG0020 events0 affected18 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0024 events2 affected18 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected30 at risk EG0021 events1 affected18 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected30 at risk EG0021 events1 affected18 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected30 at risk EG0024 events1 affected18 at risk
Headache	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected30 at risk EG0022 events2 affected18 at risk
Neurotoxicity	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0021 events1 affected18 at risk
Rash vesicular	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0021 events1 affected18 at risk
Skin necrosis	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected30 at risk EG0021 events1 affected18 at risk

ID	Term
D000380	Agranulocytosis
D007970	Leukopenia
D000095542	Cytopenia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007960	Leukocyte Disorders

ID	Term
D016179	Granulocyte Colony-Stimulating Factor
D003115	Colony-Stimulating Factors
D006023	Glycoproteins
D006001	Glycoconjugates
D002241	Carbohydrates
D016298	Hematopoietic Cell Growth Factors
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D001685	Biological Factors

ID	Title	Description
BG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
BG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
BG002	Adolescents (12 to <16 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Infants (1 Month to <2 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.	2	0	2	2	2
EG001	Children (2 to <12 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.	30	9	30	27	30
EG002	Adolescents (12 to <16 Years)	Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.	18	3	18	15	18