SPI-2012 vs Pegfilgrastim in the Management of Neutropeni... | NCT02643420

Label	Type	Description	Intervention Names
Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)	Experimental	Participants received SPI-2012 13.2 milligram (mg)/0.6 milliliter (mL) (3.6 mg Granulocyte Colony-Stimulating Factor [G-CSF]) fixed-dose subcutaneous (SC) injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 intravenous (IV) infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Drug: SPI-2012 Drug: Docetaxel Drug: Cyclophosphamide
Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)	Experimental	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Drug: Pegfilgrastim Drug: Docetaxel Drug: Cyclophosphamide

Name	Type	Description	Arm Group Labels	Other Names
SPI-2012	Drug	Single-use syringes for subcutaneous injection, administered on Day 2 of each cycle	Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)

Measure	Description	Time Frame
Duration of Severe Neutropenia (DSN) in Cycle 1	DSN was defined as the number of days of severe neutropenia (absolute neutrophil count [ANC] <0.5×10^9/L), after the administration of study drug in Cycle 1.	Day 1 and Days 4-15 in Cycle 1 (each cycle was 21 days)

Measure	Description	Time Frame
Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1	Time to ANC Recovery was defined as the time from chemotherapy administration until ANC increased to ≥1.5×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was assigned as 0 for participants whose ANC value never dropped below 1.5 x10^9/L.	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Center for Cancer Care		Glendale	Arizona	85306	United States
Arizona Clinical Research Center/ ACRC

ID	Title	Description
FG000	Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)	Participants received SPI-2012 13.2 milligram (mg)/0.6 milliliter (mL) (3.6 mg Granulocyte Colony-Stimulating Factor [G-CSF]) fixed-dose subcutaneous (SC) injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 intravenous (IV) infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 26, 2017	Dec 23, 2021

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

Duration of Severe Neutropenia (DSN) in Cycle 1

DSN was defined as the number of days of severe neutropenia (absolute neutrophil count [ANC] <0.5×10^9/L), after the administration of study drug in Cycle 1.

The ITT population included all participants who were randomized.

Posted

Mean

Standard Deviation

days

Day 1 and Days 4-15 in Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 and TC	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
OG001	Arm 2: Pegfilgrastim and TC	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.

Units	Counts
Participants	OG000196 OG001210

Title

Denominators

Categories

Title	Measurements
	OG0000.20± 0.503 OG0010.35± 0.683

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-statistics	The p-values are based on the calculated t-statistics from the bootstrapped sample mean and standard deviation.	<0.0001		Mean Difference (Final Values)	-0.148			2-Sided	95	-0.266	-0.031					Non-Inferiority	The margin of non-inferiority to be used in the study is 0.62 day. The non-inferiority of SPI-2012 to Pegfilgrastim was declared if the upper bound of 95% confidence interval (CI) of the difference in mean DSN between the treatment arms was <0.62 days.

Secondary

Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1

Time to ANC Recovery was defined as the time from chemotherapy administration until ANC increased to ≥1.5×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was assigned as 0 for participants whose ANC value never dropped below 1.5 x10^9/L.

The ITT population included all participants who were randomized.

Posted

Mean

Standard Deviation

days

Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 and TC	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
OG001	Arm 2: Pegfilgrastim and TC	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.

Secondary

Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1

Depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or Pegfilgrastim) in Cycle 1.

The ITT population included all participants who were randomized. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

10^9 ANC/L

Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 and TC	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
OG001	Arm 2: Pegfilgrastim and TC	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.

Secondary

Number of Participants With Febrile Neutropenia (FN) in Cycle 1

FN was defined as an oral temperature > 38.3 degrees Celsius (C) (101.0 degrees Fahrenheit [F]) or two consecutive readings of >=38.0 degrees C (100.4 degrees F) for 2 hours and ANC <1.0×10^9/L.

The ITT population included all participants who were randomized.

Posted

Count of Participants

Participants

Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 and TC	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
OG001	Arm 2: Pegfilgrastim and TC	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.

Secondary

Duration of Severe Neutropenia in Cycle 2, 3 and 4

DSN was defined as the number of days of severe neutropenia (ANC <0.5×10^9 /L) from the first occurrence of an ANC below the threshold in Cycles 2, 3, and 4.

The ITT population included all participants who were randomized.

Posted

Mean

Standard Deviation

days

Days 1, 4, 7, 10, and 15 in cycles 2, 3, and 4 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 and TC	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
OG001	Arm 2: Pegfilgrastim and TC	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.

Secondary

Number of Participants With Neutropenic Complications in Cycle 1

Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia.

The ITT population included all participants who was randomized.

Posted

Count of Participants

Participants

Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 and TC	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
OG001	Arm 2: Pegfilgrastim and TC	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.

Secondary

Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4

FN was defined as an oral temperature > 38.3 degrees C (101.0 degrees Fahrenheit [F]) or two consecutive readings of >=38.0 degrees C (100.4 degrees F) for 2 hours and ANC <1.0×10^9/L.

The ITT population included all participants who were randomized

Posted

Count of Participants

Participants

Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 and TC	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
OG001	Arm 2: Pegfilgrastim and TC	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.

Secondary

Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4

RDI was defined as the percentage of the planned dose that each participant actually received during the study, expressed as the total dose received, divided by the total dose planned and multiplied by 100. The planned dose was defined as the dose that would be given if no doses were missed and/or no dose reductions were made for the number of cycles started. The total planned dose was the sum of planned doses over all cycles.

Safety Population included all participants who received at least one dose of any protocol-specified drug (TC, SPI-2012 or pegfilgrastim). One participant was randomized to pegfilgrastim but was given SPI-2012 in Safety Population.

Posted

Mean

Standard Deviation

percentage of planned dose

Cycles 1 to 4 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 and TC	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
OG001	Arm 2: Pegfilgrastim and TC	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product or study procedure, whether or not considered related to the medicinal product. A TEAE for Treatment Period is defined as adverse event with an onset date on or after the date of study drug administration through the end of treatment. TEAE for follow up is defined as any new onset or ongoing AE at the end of Treatment. SAE is defined as any AE which meets any of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in a persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, includes important medical events.

Posted

Count of Participants

Participants

From the first dose of TC (Docetaxel + Cyclophosphamide) until 12 months after the last dose of study treatment (up to approximately 34 months)

ID	Title	Description
OG000	Arm 1: SPI-2012 and TC -Treatment Period	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after the last study treatment or patient discontinuation.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected197 at risk EG0012 affected208 at risk EG0021 affected197 at risk EG0030 affected208 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0012 affected208 at risk EG0021 affected197 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0012 affected208 at risk EG0020 affected197 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Ventricular arrhythmia	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0012 affected208 at risk EG0021 affected197 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0012 affected208 at risk EG0020 affected197 at risk EG003
Gastrointestinal ischaemia	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Gastrointestinal necrosis	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Neutropenic colitis	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0013 affected208 at risk EG0020 affected197 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0021 affected197 at risk EG003
Pyrexia	General disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected197 at risk EG0016 affected208 at risk EG0021 affected197 at risk EG003
Asthenia	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Chest pain	General disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Multi-organ failure	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Oedema peripheral	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Pain	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Cellulitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0021 affected197 at risk EG003
Incision site cellulitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0010 affected208 at risk EG0021 affected197 at risk EG003
Breast cellulitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Bronchitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0012 affected208 at risk EG0020 affected197 at risk EG003
Clostridium difficile sepsis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Colonic abscess	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0002 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Device related infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Diverticulitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0002 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Influenza	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Lung infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Pneumonia	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0002 affected197 at risk EG0013 affected208 at risk EG0020 affected197 at risk EG003
Rectal abscess	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Sepsis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0002 affected197 at risk EG0013 affected208 at risk EG0020 affected197 at risk EG003
Septic shock	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Urosepsis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Wound infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Blood lactic acid increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Body temperature increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
White blood cell count increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0012 affected208 at risk EG0020 affected197 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Headache	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Seizure	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Syncope	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected197 at risk EG0012 affected208 at risk EG0020 affected197 at risk EG003
Psychiatric decompensation	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected197 at risk EG0010 affected208 at risk EG0021 affected197 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Non-cardiogenic pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0012 affected208 at risk EG0020 affected197 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0010 affected208 at risk EG0020 affected197 at risk EG003
Hypersensitivity vasculitis	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Arteriosclerosis	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Hypertension	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Hypotension	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0011 affected208 at risk EG0020 affected197 at risk EG003
Embolism	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0010 affected208 at risk EG0021 affected197 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fatigue	General disorders	MedDRA (18.0)	Systematic Assessment	EG000120 affected197 at risk EG001124 affected208 at risk EG00214 affected197 at risk EG0038 affected208 at risk
Pyrexia	General disorders	MedDRA (18.0)	Systematic Assessment	EG00045 affected197 at risk EG00145 affected208 at risk EG0020 affected197 at risk EG003
Oedema peripheral	General disorders	MedDRA (18.0)	Systematic Assessment	EG00036 affected197 at risk EG00128 affected208 at risk EG0023 affected197 at risk EG003
Pain	General disorders	MedDRA (18.0)	Systematic Assessment	EG00031 affected197 at risk EG00130 affected208 at risk EG0021 affected197 at risk EG003
Asthenia	General disorders	MedDRA (18.0)	Systematic Assessment	EG00016 affected197 at risk EG00118 affected208 at risk EG0021 affected197 at risk EG003
Mucosal inflammation	General disorders	MedDRA (18.0)	Systematic Assessment	EG00014 affected197 at risk EG00110 affected208 at risk EG0020 affected197 at risk EG003
Chills	General disorders	MedDRA (18.0)	Systematic Assessment	EG00011 affected197 at risk EG0019 affected208 at risk EG0021 affected197 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG000112 affected197 at risk EG001104 affected208 at risk EG00211 affected197 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00087 affected197 at risk EG00186 affected208 at risk EG0023 affected197 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00062 affected197 at risk EG00148 affected208 at risk EG0022 affected197 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00040 affected197 at risk EG00134 affected208 at risk EG0024 affected197 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00026 affected197 at risk EG00125 affected208 at risk EG0023 affected197 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00020 affected197 at risk EG00125 affected208 at risk EG0020 affected197 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00020 affected197 at risk EG00117 affected208 at risk EG0025 affected197 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00011 affected197 at risk EG00115 affected208 at risk EG0021 affected197 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00013 affected197 at risk EG00112 affected208 at risk EG0020 affected197 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00012 affected197 at risk EG00113 affected208 at risk EG0021 affected197 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00071 affected197 at risk EG00170 affected208 at risk EG0026 affected197 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00048 affected197 at risk EG00136 affected208 at risk EG00220 affected197 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00041 affected197 at risk EG00140 affected208 at risk EG0024 affected197 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00043 affected197 at risk EG00126 affected208 at risk EG0023 affected197 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00022 affected197 at risk EG00131 affected208 at risk EG0028 affected197 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00012 affected197 at risk EG0018 affected208 at risk EG0020 affected197 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0006 affected197 at risk EG00111 affected208 at risk EG0024 affected197 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00095 affected197 at risk EG00193 affected208 at risk EG0022 affected197 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00032 affected197 at risk EG00144 affected208 at risk EG0023 affected197 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00020 affected197 at risk EG00119 affected208 at risk EG0022 affected197 at risk EG003
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00011 affected197 at risk EG00119 affected208 at risk EG0020 affected197 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0008 affected197 at risk EG00114 affected208 at risk EG0024 affected197 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0009 affected197 at risk EG00113 affected208 at risk EG0020 affected197 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00010 affected197 at risk EG00111 affected208 at risk EG0020 affected197 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG00080 affected197 at risk EG00174 affected208 at risk EG0022 affected197 at risk EG003
White blood cell count decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG00048 affected197 at risk EG00143 affected208 at risk EG0021 affected197 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG00035 affected197 at risk EG00138 affected208 at risk EG0020 affected197 at risk EG003
White blood cell count increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG00029 affected197 at risk EG00120 affected208 at risk EG0020 affected197 at risk EG003
Platelet count decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG00019 affected197 at risk EG0019 affected208 at risk EG0020 affected197 at risk EG003
Neutrophil count increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG00013 affected197 at risk EG00111 affected208 at risk EG0020 affected197 at risk EG003
Headache	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG00059 affected197 at risk EG00155 affected208 at risk EG0025 affected197 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG00036 affected197 at risk EG00129 affected208 at risk EG0020 affected197 at risk EG003
Dizziness	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG00037 affected197 at risk EG00123 affected208 at risk EG0027 affected197 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG00015 affected197 at risk EG00124 affected208 at risk EG0029 affected197 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG00067 affected197 at risk EG00165 affected208 at risk EG0021 affected197 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG00051 affected197 at risk EG00139 affected208 at risk EG0023 affected197 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG00019 affected197 at risk EG00122 affected208 at risk EG0020 affected197 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG00013 affected197 at risk EG00114 affected208 at risk EG0021 affected197 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0009 affected197 at risk EG0015 affected208 at risk EG0020 affected197 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG00038 affected197 at risk EG00126 affected208 at risk EG0023 affected197 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG00032 affected197 at risk EG00131 affected208 at risk EG0027 affected197 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG00021 affected197 at risk EG00125 affected208 at risk EG0021 affected197 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG00010 affected197 at risk EG00118 affected208 at risk EG0021 affected197 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG00010 affected197 at risk EG0014 affected208 at risk EG0020 affected197 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00019 affected197 at risk EG00123 affected208 at risk EG0023 affected197 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG00038 affected197 at risk EG00131 affected208 at risk EG0020 affected197 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG00022 affected197 at risk EG00121 affected208 at risk EG0020 affected197 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG00022 affected197 at risk EG00113 affected208 at risk EG0020 affected197 at risk EG003
Hot flush	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG00021 affected197 at risk EG00122 affected208 at risk EG00215 affected197 at risk EG003
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected197 at risk EG0014 affected208 at risk EG00210 affected197 at risk EG003
Lacrimation increased	Eye disorders	MedDRA (18.0)	Systematic Assessment	EG0009 affected197 at risk EG0019 affected208 at risk EG0020 affected197 at risk EG003
Tachycardia	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG00011 affected197 at risk EG00110 affected208 at risk EG0021 affected197 at risk EG003
Breast pain	Reproductive system and breast disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected197 at risk EG00110 affected208 at risk EG0029 affected197 at risk EG003

ID	Term
D000380	Agranulocytosis
D007970	Leukopenia
D000095542	Cytopenia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007960	Leukocyte Disorders
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D063088	Phosphoramides
D009943	Organophosphorus Compounds

ID	Title	Description
BG000	Arm 1: SPI-2012 and TC	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
BG001	Arm 2: Pegfilgrastim and TC	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm 1: SPI-2012 and TC -Treatment Period	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after the last study treatment or patient discontinuation.	0	197	36	197	192	197
EG001	Arm 2: Pegfilgrastim and TC -Treatment Period	Participants received Pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after the last study treatment or patient discontinuation.	1	208	29	208	203	208
EG002	Arm 1: SPI-2012 and TC - Follow up Period	In addition to the treatment period, long-term safety follow-up continued for 12 months after last dose of study treatment.	0	197	8	197	92	197
EG003	Arm 2: Pegfilgrastim and TC - Follow up Period	In addition to the treatment period, long-term safety follow-up continued for 12 months after last dose of study treatment.	1	208	2	208	82	208

ID	Term
C583329	eflapegrastim
C455861	pegfilgrastim
D000077143	Docetaxel
D003520	Cyclophosphamide