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Clinical Trial Results:
Phase 2, Open-Label, Dose-Ranging Study of HM10460A or Pegfilgrastim use for the Management of Neutropenia in Patients with Breast Cancer who are Candidates for Adjuvant and Neoadjuvant Chemotherapy with the Docetaxel + Cyclophosphamide (TC) Regimen.

Summary
EudraCT number	2013-003094-10
Trial protocol	CZ PL HU
Global end of trial date	16 Aug 2014

Results information
Results version number	v1(current)
This version publication date	03 Sep 2020
First version publication date	03 Sep 2020
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

SPI-GCF-12-201

ISRCTN number

US NCT number

NCT01724866

WHO universal trial number (UTN)

Sponsor organisation name

Spectrum Pharmaceuticals, Inc

Sponsor organisation address

157 Technology Drive, Irvine, United States, CA 92618

Public contact

Spectrum Pharmaceuticals, Spectrum Pharmaceuticals, clinicaltrialinquiries@sppirx.com

Scientific contact

Dr. Shanta Chawla, Spectrum Pharmaceuticals, shanta.chawla@sppirx.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

19 Feb 2016

Is this the analysis of the primary completion data?

Yes

Primary completion date

12 Aug 2014

Global end of trial reached?

Yes

Global end of trial date

16 Aug 2014

Was the trial ended prematurely?

Main objective of the trial

The primary objective and endpoint of this study is to assess the effect of test doses of HM10460A on the Duration of Severe Neutropenia (DSN) during Cycle 1 in patients with breast cancer who are candidates for adjuvant or neoadjuvant chemotherapy.

Protection of trial subjects

This study was conducted in accordance with Good Clinical Practice (GCP) and in line with the requirements of national legislation. Research sites were provided with protocol and product-related training. Patients were closely monitored by investigator site staff to track any adverse drug reactions.

Background therapy

N/A

Evidence for comparator

N/A

Actual start date of recruitment

25 Mar 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 13

Country: Number of subjects enrolled

Hungary: 60

Country: Number of subjects enrolled

Israel: 2

Country: Number of subjects enrolled

Australia: 21

Country: Number of subjects enrolled

United States: 46

Country: Number of subjects enrolled

Georgia: 6

Worldwide total number of subjects

148

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

101

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Countries that recruited patients to the trial were Australia, Georgia, Israel, Poland, Hungary and United States. Since no patients eventually enrolled from Czech Republic, this country was removed.

Screening details

Patient eligibility during the trial was assessed according to the eligibility criteria within the current version of the protocol at the time the patient was enrolled.

Number of subjects started

148

Number of subjects completed

147

Reason: Number of subjects

Consent withdrawn by subject: 1

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

It was an open-label study and hence no blinding was used.

Are arms mutually exclusive

Yes

SPI-2012 (45 µg/kg)

Arm description

Patients receiving 45 µg/kg SPI-2012.

Arm type

Experimental

Investigational medicinal product name

SPI-2012

Investigational medicinal product code

Other name

HM10460A

Pharmaceutical forms

Solution for injection/infusion in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Dosage of 45 µg/kg SPI-2012 was administered to patients in Arm 1. The dose was calculated based on the patient's weight on Day 1 of each cycle. The appropriate volume was drawn directly from the syringe according to the patient's weight. SPI-2012 was administered subcutaneously once per chemotherapy cycle on Day 2 (approx. 24 hours [± 2 hours] after chemotherapy). SPI-2012 could be administered using a push time consistent with the Institutional Standard of Care for Neulasta (Pegfilgrastim).

SPI-2012 (135 µg/kg)

Arm description

Patients receiving 135 µg/kg SPI-2012.

Arm type

Experimental

Investigational medicinal product name

SPI-2012

Investigational medicinal product code

Other name

HM10460A

Pharmaceutical forms

Solution for injection/infusion in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Dosage of 135 µg/kg SPI-2012 was administered to patients in Arm 2. The dose was calculated based on the patient's weight on Day 1 of each cycle. The appropriate volume was drawn directly from the syringe according to the patient's weight. SPI-2012 was administered subcutaneously once per chemotherapy cycle on Day 2 (approx. 24 hours [± 2 hours] after chemotherapy). SPI-2012 could be administered using a push time consistent with the Institutional Standard of Care for Neulasta (Pegfilgrastim).

SPI-2012 (270 µg/kg)

Arm description

Patients receiving 270 µg/kg SPI-2012

Arm type

Experimental

Investigational medicinal product name

SPI-2012

Investigational medicinal product code

Other name

HM10460A

Pharmaceutical forms

Solution for injection/infusion in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Dosage of 270 µg/kg SPI-2012 was administered to patients in Arm 3. The dose was calculated based on the patient's weight on Day 1 of each cycle. The appropriate volume was drawn directly from the syringe according to the patient's weight. SPI-2012 was administered subcutaneously once per chemotherapy cycle on Day 2 (approx. 24 hours [± 2 hours] after chemotherapy). SPI-2012 could be administered using a push time consistent with the Institutional Standard of Care for Neulasta (Pegfilgrastim).

Pegfilgrastim (6 mg per PI)

Arm description

Patients receiving Pegfilgrastim (6 mg per manufacturer's prescribing information)

Arm type

Active comparator

Investigational medicinal product name

Pegfilgrastrim

Investigational medicinal product code

Other name

Neulasta

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Pegfilgrastrim was administered according to manufacturer's PI (6 mg subcutaneously once per chemotherapy cycle on Day 2 approximately 24 hours after chemotherapy).

Number of subjects in period 1 ^[1]	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Started	39	36	36	36
Completed	38	32	33	35
Not completed	1	4	3	1
Physician decision	1	1	1	-
Consent withdrawn by subject	-	1	1	-
Adverse event, non-fatal	-	-	1	1
Protocol deviation	-	2	-	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: One of the subjects withdrew consent before receiving SPI-2012 treatment and thus was not included in the efficacy population.

Baseline characteristics

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Reporting group title

SPI-2012 (45 µg/kg)

Reporting group description

Patients receiving 45 µg/kg SPI-2012.

Reporting group title

SPI-2012 (135 µg/kg)

Reporting group description

Patients receiving 135 µg/kg SPI-2012.

Reporting group title

SPI-2012 (270 µg/kg)

Reporting group description

Patients receiving 270 µg/kg SPI-2012

Reporting group title

Pegfilgrastim (6 mg per PI)

Reporting group description

Patients receiving Pegfilgrastim (6 mg per manufacturer's prescribing information)

Reporting group values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)	Total
Number of subjects	39	36	36	36	147
Age categorical
Units: Subjects
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0
Adults (18-64 years)	24	25	30	21	100
From 65-84 years	15	11	6	15	47
85 years and over	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	59.8 ± 11.31	56.8 ± 10.63	55.7 ± 9.79	60.4 ± 10.43	-
Gender categorical
Units: Subjects
Female	39	35	34	36	144
Male	0	1	2	0	3
Race
Units: Subjects
American Indian or Alaska Native	1	0	0	0	1
Asian	0	0	1	0	1
Black or African American	2	0	0	0	2
White	36	36	35	32	139
Others	0	0	0	4	4
Ethnicity
Units: Subjects
Hispanic or Latino	6	2	2	4	14
Not Hispanic or Latino	33	34	34	32	133
ECOG
Units: Subjects
0- Fully active	33	32	35	33	133
1-Restricted	5	4	1	2	12
2-Ambulatory	1	0	0	0	1
Missing	0	0	0	1	1
Weight
Units: kg
arithmetic mean (standard deviation)	77.2 ± 13.18	75.6 ± 23.06	76.5 ± 17.57	78 ± 17.2	-
Height
Units: cm
arithmetic mean (standard deviation)	162.0 ± 8.19	161.6 ± 6.61	163.0 ± 8.06	159.6 ± 9.88	-
BSA
Units: m2
arithmetic mean (standard deviation)	1.83 ± 0.17	1.81 ± 0.27	1.83 ± 0.21	1.83 ± 0.22	-

End points

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Reporting group title

SPI-2012 (45 µg/kg)

Reporting group description

Patients receiving 45 µg/kg SPI-2012.

Reporting group title

SPI-2012 (135 µg/kg)

Reporting group description

Patients receiving 135 µg/kg SPI-2012.

Reporting group title

SPI-2012 (270 µg/kg)

Reporting group description

Patients receiving 270 µg/kg SPI-2012

Reporting group title

Pegfilgrastim (6 mg per PI)

Reporting group description

Patients receiving Pegfilgrastim (6 mg per manufacturer's prescribing information)

Primary: Duration of severe neutropenia (DSN) in Cycle 1

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End point title

Duration of severe neutropenia (DSN) in Cycle 1

End point description

DSN was defined as the interval from the day of first observation of Grade 4 neutropenia (ANC < 0.5 x 10^9/L ) to the first ANC recovery to ≥ 2.0 x 10^9/L in Cycle 1. Treatment differences in DSN in Cycle 1 were analysed using confidence intervals (CIs) based upon 10,000 bootstrap samples stratified by baseline weight (<65 kg, ≥ 65 kg and ≤ 75 kg or >75 kg). For each sample, the difference between treatment arms was calculated. Two-sided CIs and p-values were used to calculate the difference in mean DSN of patients between any 2 arms.

End point type

Primary

End point timeframe

Twenty-one (21) days of Cycle 1 where chemotherapy was administered on Day 1 followed by SPI-2012 administration on Day 2 [24 hours (± 2 hrs)].

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	39	36	36	36
Units: days
arithmetic mean (standard deviation)	1.03 ± 1.547	0.44 ± 1.275	0.03 ± 0.167	0.31 ± 0.822

Comparision of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling. Number of subjects 75, includes 39 SPI-2012 (45 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

P-value

= 0.296 ^[2]

Method

Bootstrap method

Parameter type

Mean difference (final values)

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.19

upper limit

1.27

Variability estimate

Standard deviation

Notes
[1] - Non-inferiority was demonstrated if the upper CI was < 1 day. Unit for point estimate is days.
[2] - The p-value does not support the hypothesis for non-inferiority.

Comparision of SPI-2012(135µg/kg) vs Pegfilgrastim

Statistical analysis description

A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling. Number of subjects 72, includes 36 SPI-2012 (135 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

Pegfilgrastim (6 mg per PI) v SPI-2012 (135 µg/kg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

P-value

= 0.002 ^[4]

Method

Bootstrap method

Parameter type

Mean difference (final values)

Point estimate

0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

0.64

Variability estimate

Standard deviation

Notes
[3] - Non-inferiority was demonstrated if the upper CI was < 1 day. Unit for point estimate is days.
[4] - Non-inferiority can be established due to p < 0.05.

Comparision of SPI-2012(270µg/kg) vs Pegfilgrastim

Statistical analysis description

A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-values was calculated as two times the proportion of treatment difference greater than 1 in the resampling. Number of subjects 72, includes 36 SPI-2012 (270 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

Pegfilgrastim (6 mg per PI) v SPI-2012 (270 µg/kg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

P-value

< 0.001 ^[6]

Method

Bootstrap method

Parameter type

Mean difference (final values)

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.56

upper limit

-0.06

Variability estimate

Standard deviation

Notes
[5] - Non-inferiority was demonstrated if the upper CI was < 1 day. Unit for point estimate is days.
[6] - Non-inferiority can be established due to p < 0.05.

Secondary: Duration of severe neutropenia (DSN) in Cycle 2

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End point title

Duration of severe neutropenia (DSN) in Cycle 2

End point description

DSN was defined as the interval from the day of first observation of Grade 4 neutropenia (ANC < 0.5 x 10^9/L ) to the first ANC recovery to ≥ 2.0 x 10^9/L in Cycle 2. Treatment differences in DSN in Cycle 2 were analysed using confidence intervals (CIs) based upon 10,000 bootstrap samples stratified by baseline weight (<65 kg, ≥ 65 kg and ≤ 75 kg or >75 kg). For each sample, the difference between treatment arms was calculated. Two-sided CIs and p-values were used to calculate the difference in mean DSN of patients between any 2 arms.

End point type

Secondary

End point timeframe

Twenty-one (21) days of Cycle 2. Chemotherapy in Cycle 2 was begun on Day 1 when the patient had recovered to ANC values > 2 x10^9/L and platelet count ≥100x10^9/L from Cycle 1.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	39	34	34	36
Units: days
arithmetic mean (standard deviation)	0.46 ± 1.022	0.12 ± 0.478	0.03 ± 0.171	0.08 ± 0.368

Comparison of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

P-value

= 0.001 ^[8]

Method

Bootstrap method

Parameter type

Mean difference (final values)

Point estimate

0.38

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

0.74

Variability estimate

Standard deviation

Notes
[7] - Non-inferiority was demonstrated if the upper CI was < 1 day. Unit for point estimate is days.
[8] - Non-inferiority can be established due to p < 0.05.

Comparison of SPI-2012 (135µg/kg) vs Pegfilgrastim

Statistical analysis description

A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling. Number of subjects 70, includes 34 SPI-2012 (135 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

Pegfilgrastim (6 mg per PI) v SPI-2012 (135 µg/kg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

P-value

< 0.001 ^[10]

Method

Bootstrap method

Parameter type

Mean difference (final values)

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.24

Variability estimate

Standard deviation

Notes
[9] - Non-inferiority was demonstrated if the upper CI was < 1 day. Unit for point estimate is days.
[10] - Non-inferiority can be established due to p < 0.05.

Comparison of SPI-2012 (270µg/kg) vs Pegfilgrastim

Statistical analysis description

A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling. Number of subjects 70, includes 34 SPI-2012 (270 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

Pegfilgrastim (6 mg per PI) v SPI-2012 (270 µg/kg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

P-value

< 0.001 ^[12]

Method

Bootstrap method

Parameter type

Mean difference (final values)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.06

Variability estimate

Standard deviation

Notes
[11] - Non-inferiority was demonstrated if the upper CI was < 1 day. Unit for point estimate is days.
[12] - Non-inferiority can be established due to p < 0.05.

Secondary: Duration of severe neutropenia (DSN) in Cycle 3

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End point title

Duration of severe neutropenia (DSN) in Cycle 3

End point description

DSN was defined as the interval from the day of first observation of Grade 4 neutropenia (ANC < 0.5 x 10^9/L ) to the first ANC recovery to ≥ 2.0 x 10^9/L in Cycle 3. Treatment differences in DSN in Cycle 3 were analysed using confidence intervals (CIs) based upon 10,000 bootstrap samples stratified by baseline weight (<65 kg, ≥ 65 kg and ≤ 75 kg or >75 kg). For each sample, the difference between treatment arms was calculated. Two-sided CIs and p-values were used to calculate the difference in mean DSN of patients between any 2 arms.

End point type

Secondary

End point timeframe

Twenty-one (21) days of Cycle 3. Chemotherapy in Cycle 3 was begun on Day 1 when the patient had recovered to ANC values > 2 x10^9/L and platelet count ≥100x10^9/L from Cycle 2.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	38	32	34	36
Units: days
arithmetic mean (standard deviation)	0.45 ± 1.132	0.16 ± 0.628	0.15 ± 0.610	0.14 ± 0.593

Comparision of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling. Number of subjects 74, includes 38 SPI-2012 (45 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

P-value

= 0.002 ^[14]

Method

Bootstrap method

Parameter type

Mean difference (final values)

Point estimate

0.31

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07

upper limit

0.72

Variability estimate

Standard deviation

Notes
[13] - Non-inferiority was demonstrated if the upper CI was < 1 day. Unit for point estimate is days.
[14] - Non-inferiority can be established due to p < 0.05.

Comparison of SPI-2012 (135µg/kg) vs Pegfilgrastim

Statistical analysis description

A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling. Number of subjects 68, includes 32 SPI-2012 (135 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

SPI-2012 (135 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

P-value

< 0.001 ^[16]

Method

Bootstrap method

Parameter type

Mean difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.3

Variability estimate

Standard deviation

Notes
[15] - Non-inferiority was demonstrated if the upper CI was < 1 day. Unit for point estimate is days.
[16] - Non-inferiority can be established due to p < 0.05.

Comparison of SPI-2012 (270µg/kg) vs Pegfilgrastim

Statistical analysis description

A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling. Number of subjects 70, includes 34 SPI-2012 (270 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

Pegfilgrastim (6 mg per PI) v SPI-2012 (270 µg/kg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[17]

P-value

< 0.001 ^[18]

Method

Bootstrap method

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.28

Variability estimate

Standard deviation

Notes
[17] - Non-inferiority was demonstrated if the upper CI was < 1 day. Unit for point estimate is days.
[18] - Non-inferiority can be established due to p < 0.05.

Secondary: Duration of severe neutropenia (DSN) in Cycle 4

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End point title

Duration of severe neutropenia (DSN) in Cycle 4

End point description

DSN was defined as the interval from the day of first observation of Grade 4 neutropenia (ANC < 0.5 x 10^9/L ) to the first ANC recovery to ≥ 2.0 x 10^9/L in Cycle 4. Treatment differences in DSN in Cycle 4 were analysed using confidence intervals (CIs) based upon 10,000 bootstrap samples stratified by baseline weight (<65 kg, ≥ 65 kg and ≤ 75 kg or >75 kg). For each sample, the difference between treatment arms was calculated. Two-sided CIs and p-values were used to calculate the difference in mean DSN of patients between any 2 arms.

End point type

Secondary

End point timeframe

Twenty-one (21) days of Cycle 4. Chemotherapy in Cycle 4 was begun on Day 1 when the patient had recovered to ANC values > 2 x10^9/L and platelet count ≥100x10^9/L from Cycle 3.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	38	32	33	35
Units: day
arithmetic mean (standard deviation)	1.05 ± 4.579	0.19 ± 0.738	0.09 ± 0.522	0.11 ± 0.404

Comparison of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling. Number of subjects 73, includes 38 SPI-2012 (45 μg/kg) and 35 (Pegfilgrastim).

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

P-value

= 0.781 ^[20]

Method

Bootstrap method

Parameter type

Mean difference (final values)

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

2.47

Variability estimate

Standard deviation

Notes
[19] - Non-inferiority was demonstrated if the upper CI was < 1 day. Unit for point estimate is days.
[20] - The p-value does not support the hypothesis for non-inferiority

Comparison of SPI-2012 (135µg/kg) vs Pegfilgrastim

Statistical analysis description

A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling. Number of subjects 67, includes 32 SPI-2012 (135 μg/kg) and 35 (Pegfilgrastim).

Comparison groups

SPI-2012 (135 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

P-value

< 0.001 ^[22]

Method

Bootstrap method

Parameter type

Mean difference (final values)

Point estimate

0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.17

upper limit

0.38

Variability estimate

Standard deviation

Notes
[21] - Non-inferiority was demonstrated if the upper CI was < 1 day. Unit for point estimate is days.
[22] - Non-inferiority can be established due to p < 0.05.

Comparison of SPI-2012 (270µg/kg) vs Pegfilgrastim

Statistical analysis description

A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling. Number of subjects 68, includes 33 SPI-2012 (270 μg/kg) and 35 (Pegfilgrastim).

Comparison groups

SPI-2012 (270 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

P-value

< 0.001 ^[24]

Method

Boot-strap method

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.23

upper limit

0.22

Variability estimate

Standard deviation

Notes
[23] - Non-inferiority was demonstrated if the upper CI was < 1 day. Unit for point estimate is days.
[24] - Non-inferiority can be established due to p < 0.05.

Secondary: Time to ANC recovery in Cycle 1

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End point title

Time to ANC recovery in Cycle 1

End point description

The time to ANC recovery was calculated form the date of chemotherapy through to date that their ANC values increased to ≥2.0 x 10^9/L. Time to ANC recovery was calculated for only those patients whose ANC values dropped below <2.0 x 10^9/L.

End point type

Secondary

End point timeframe

Twenty-one (21) days of Cycle 1.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	29	14	6	14
Units: days
median (confidence interval 95%)	10 (10.0 to 11.0)	8.5 (8.0 to 9.0)	8 (7.0 to 9.0)	9 (8.0 to 10.0)

Comparison of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

Treatment effect was compared by a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI. Number of subjects 43, includes 29 SPI-2012 (45 μg/kg) and 14 (Pegfilgrastim).

Comparison groups

Pegfilgrastim (6 mg per PI) v SPI-2012 (45 µg/kg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[25]

P-value

= 0.002 ^[26]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

1.8

Variability estimate

Standard error of the mean

Notes
[25] - Unit for point estimate is days.
[26] - There is a statistically significant difference between SPI-2012 (45 µg/kg) and Pegfilgrastim to the advantage of Pegfilgrastim.

Comparison of SPI-2012 (135µg/kg) vs Pegfilgrastim

Statistical analysis description

Treatment effect was compared by a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI. Number of subjects 28, includes 14 SPI-2012 (135 μg/kg) and 14 (Pegfilgrastim).

Comparison groups

SPI-2012 (135 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[27]

P-value

= 0.711 ^[28]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.4

Variability estimate

Standard error of the mean

Notes
[27] - Unit for point estimate is days.
[28] - There is no statistically significant difference between SPI-2012 (135µg/kg) and Pegfilgrastim.

Comparison of SPI-2012 (270µg/kg) vs Pegfilgrastim

Statistical analysis description

Treatment effect was compared by a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI. Number of subjects 20, includes 6 SPI-2012 (270 μg/kg) and 14 (Pegfilgrastim).

Comparison groups

SPI-2012 (270 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[29]

P-value

= 0.028 ^[30]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.9

Variability estimate

Standard error of the mean

Notes
[29] - Unit for point estimate is days.
[30] - There is a statistically significant difference between SPI-2012 (270 µg/kg) and Pegfilgrastim to the advantage of SPI-2012.

Secondary: Time to ANC recovery in Cycle 2

Top of page

End point title

Time to ANC recovery in Cycle 2

End point description

End point type

Secondary

End point timeframe

Twenty-one (21) days of Cycle 2.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	23	8	7	10
Units: day
median (confidence interval 95%)	11.0 (10.0 to 11.0)	9.5 (8.0 to 10.0)	10.0 (8.0 to 14.0)	10.0 (8.0 to 11.0)

Comparison of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

Treatment effect was compared by a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI. Number of subjects 33, includes 23 SPI-2012 (45 μg/kg) and 10 (Pegfilgrastim).

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[31]

P-value

= 0.672 ^[32]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.4

Variability estimate

Standard error of the mean

Notes
[31] - Unit for point estimate is days.
[32] - There is no statistically significant difference between SPI-2012 (45 µg/kg) and Pegfilgrastim.

Comparison of SPI-2012 (135µg/kg) vs Pegfilgrastim

Statistical analysis description

Treatment effect was compared by a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI. Number of subjects 18, includes 8 SPI-2012 (135 μg/kg) and 10 (Pegfilgrastim).

Comparison groups

Pegfilgrastim (6 mg per PI) v SPI-2012 (135 µg/kg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[33]

P-value

= 0.348 ^[34]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.3

Variability estimate

Standard error of the mean

Notes
[33] - Unit for point estimate is days.
[34] - There is no statistically significant difference between SPI-2012 (135µg/kg) and Pegfilgrastim.

Comparison of SPI-2012 (270µg/kg) vs Pegfilgrastim

Statistical analysis description

Treatment effect was compared by a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI. Number of subjects 17, includes 7 SPI-2012 (270 μg/kg) and 10 (Pegfilgrastim).

Comparison groups

SPI-2012 (270 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[35]

P-value

= 0.973 ^[36]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

2.9

Variability estimate

Standard error of the mean

Notes
[35] - Unit for point estimate is days.
[36] - There is no statistically significant difference between SPI-2012 (270 µg/kg) and Pegfilgrastim.

Secondary: Time to ANC recovery in Cycle 3

Top of page

End point title

Time to ANC recovery in Cycle 3

End point description

End point type

Secondary

End point timeframe

Twenty-one (21) days of Cycle 3.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	20	6	5	9
Units: day
median (confidence interval 95%)	10.0 (10.0 to 11.0)	9.5 (8.0 to 12.0)	9.0 (8.0 to 13.0)	10.0 (9.0 to 11.0)

Comparison of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

Treatment effect was compared by a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI. Number of subjects 29, includes 20 SPI-2012 (45 μg/kg) and 9 (Pegfilgrastim).

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[37]

P-value

= 0.618 ^[38]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.4

Variability estimate

Standard error of the mean

Notes
[37] - Unit for point estimate is days.
[38] - There is no statistically significant difference between SPI-2012 (45 µg/kg) and Pegfilgrastim.

Comparison of SPI-2012 (135µg/kg) vs Pegfilgrastim

Statistical analysis description

Treatment effect was compared by a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI. Number of subjects 15, includes 6 SPI-2012 (135 μg/kg) and 9 (Pegfilgrastim).

Comparison groups

SPI-2012 (135 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[39]

P-value

= 0.661 ^[40]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.6

Variability estimate

Standard error of the mean

Notes
[39] - Unit for point estimate is days.
[40] - There is no statistically significant difference between SPI-2012 (135µg/kg) and Pegfilgrastim.

Comparison of SPI-2012 (270µg/kg) vs Pegfilgrastim

Statistical analysis description

Treatment effect was compared by a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI. Number of subjects 14, includes 5 SPI-2012 (270 μg/kg) and 9 (Pegfilgrastim).

Comparison groups

SPI-2012 (270 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[41]

P-value

= 0.754 ^[42]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

2.8

Variability estimate

Standard error of the mean

Notes
[41] - Unit for point estimate is days.
[42] - There is no statistically significant difference between SPI-2012 (270 µg/kg) and Pegfilgrastim.

Secondary: Time to ANC recovery in Cycle 4

Top of page

End point title

Time to ANC recovery in Cycle 4

End point description

End point type

Secondary

End point timeframe

Twenty-one (21) days of Cycle 4.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	23	8	4	12
Units: day
median (confidence interval 95%)	11.0 (10.0 to 13.0)	10.0 (9.0 to 11.0)	10.0 (8.0 to 14.0)	10.0 (8.0 to 11.0)

Comparison of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

Treatment effect was compared by a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI. Number of subjects 35, includes 23 SPI-2012 (45 μg/kg) and 12 (Pegfilgrastim).

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[43]

P-value

= 0.009 ^[44]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

1.7

Variability estimate

Standard error of the mean

Notes
[43] - Unit for point estimate is days.
[44] - There is a statistically significant difference between SPI-2012 (45 µg/kg) and Pegfilgrastim to the advantage of Pegfilgrastim.

Comparison of SPI-2012 (135µg/kg) vs Pegfilgrastim

Statistical analysis description

Treatment effect was compared by a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI. Number of subjects 20, includes 8 SPI-2012 (135 μg/kg) and 12 (Pegfilgrastim).

Comparison groups

SPI-2012 (135 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[45]

P-value

= 0.527 ^[46]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.8

Variability estimate

Standard error of the mean

Notes
[45] - Unit for point estimate is days.
[46] - There is no statistically significant difference between SPI-2012 (135µg/kg) and Pegfilgrastim.

Comparison of SPI-2012 (270µg/kg) vs Pegfilgrastim

Statistical analysis description

Treatment effect was compared by a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI. Number of subjects 16, includes 4 SPI-2012 (270 μg/kg) and 12 (Pegfilgrastim).

Comparison groups

SPI-2012 (270 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[47]

P-value

= 0.815 ^[48]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

3.9

Variability estimate

Standard error of the mean

Notes
[47] - Unit for point estimate is days.
[48] - There is no statistically significant difference between SPI-2012 (270 µg/kg) and Pegfilgrastim.

Secondary: Depth of ANC Nadir in Cycle 1

Top of page

End point title

Depth of ANC Nadir in Cycle 1

End point description

Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir. Depth of ANC nadir was defined as the lowest ANC value in each cycle. The log10 transformation was used on the nadirs to satisfy the normality assumption. The nadir ratio between any 2 arms, associated 95% 2-sided CI and p-value assuming asymptomatic normality on the log transformed.

End point type

Secondary

End point timeframe

Twenty-one (21) days of Cycle 1.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	39	36	36	36
Units: x10^9/L
median (full range (min-max))	0.8 (0.0 to 9.0)	3.0 (0.1 to 14.1)	6.2 (0.2 to 21.0)	3.0 (0.0 to 9.1)

Comparison of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

The median depth of the ANC nadir was compared between SPI-2012 (45 µg/kg) and Pegfilgrastim. Number of subjects 75, includes 39 SPI-2012 (45 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[49]

P-value

= 0.008 ^[50]

Method

ANOVA

Parameter type

Log risk ratio

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.25

upper limit

0.8

Variability estimate

Standard error of the mean

Notes
[49] - The analysis of variance was applied to calculate the p-value and 95% confidence interval. Unit for point estimate is x10^9/L.
[50] - There is a statistically significant difference between SPI-2012 (45µg/kg) and Pegfilgrastim in which SPI-2012 has a lower nadir compared to the Pegfilgrastim arm.

Comparison of SPI-2012(135µg/kg) vs Pegfilgrastim

Statistical analysis description

The median depth of the ANC nadir was compared between SPI-2012 (135 µg/kg) and Pegfilgrastim. Number of subjects 72, includes 36 SPI-2012 (135 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

Pegfilgrastim (6 mg per PI) v SPI-2012 (135 µg/kg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[51]

P-value

= 0.911 ^[52]

Method

ANOVA

Parameter type

Log risk ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

2.04

Variability estimate

Standard error of the mean

Notes
[51] - The analysis of variance was applied to calculate the p-value and 95% confidence interval. Unit for point estimate is x10^9/L.
[52] - There is no statistically significant difference between SPI-2012 (135µg/kg) and Pegfilgrastim.

Comparison of SPI-2012(270µg/kg) vs Pegfilgrastim

Statistical analysis description

The median depth of the ANC nadir was compared between SPI-2012 (270 µg/kg) and Pegfilgrastim. Number of subjects 72, includes 36 SPI-2012 (270 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

Pegfilgrastim (6 mg per PI) v SPI-2012 (270 µg/kg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[53]

P-value

= 0.002 ^[54]

Method

ANOVA

Parameter type

Log risk ratio

Point estimate

2.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.4

upper limit

4.54

Variability estimate

Standard error of the mean

Notes
[53] - The analysis of variance was applied to calculate the p-value and 95% confidence interval. Unit for point estimate is x10^9/L.
[54] - There is statistically significant difference between SPI-2012 (270µg/kg) and Pegfilgrastim in which the SPI-2012 has a higher nadir compared to Pegfilgrastim.

Secondary: Depth of ANC Nadir in Cycle 2

Top of page

End point title

Depth of ANC Nadir in Cycle 2

End point description

End point type

Secondary

End point timeframe

Twenty-one (21) days of Cycle 2.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	39	34	34	36
Units: x10^9/L
median (full range (min-max))	1.3 (0.1 to 8.0)	3.3 (0.1 to 9.5)	4.8 (0.3 to 25.7)	2.9 (0.1 to 9.2)

Comparison of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

The median depth of the ANC nadir was compared between SPI-2012 (45 µg/kg) and Pegfilgrastim. Number of subjects 75, includes 39 SPI-2012 (45 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[55]

P-value

= 0.005 ^[56]

Method

ANOVA

Parameter type

Log risk ratio

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

0.8

Variability estimate

Standard error of the mean

Notes
[55] - The analysis of variance was applied to calculate the p-value and 95% confidence interval. Unit for point estimate is x10^9/L.
[56] - There is a statistically significant difference between SPI-2012 (45µg/kg) and Pegfilgrastim in which SPI-2012 has a lower nadir compared to the Pegfilgrastim arm.

Comparison of SPI-2012 (135µg/kg) vs Pegfilgrastim

Statistical analysis description

The median depth of the ANC nadir was compared between SPI-2012 (135 µg/kg) and Pegfilgrastim. Number of subjects 70, includes 34 SPI-2012 (135 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

SPI-2012 (135 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[57]

P-value

= 0.633 ^[58]

Method

ANOVA

Parameter type

Log risk ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.79

Variability estimate

Standard error of the mean

Notes
[57] - The analysis of variance was applied to calculate the p-value and 95% confidence interval. Unit for point estimate is x10^9/L.
[58] - There is no statistically significant difference between SPI-2012 (135µg/kg) and Pegfilgrastim.

Comparison of SPI-2012 (270µg/kg) vs Pegfilgrastim

Statistical analysis description

The median depth of the ANC nadir was compared between SPI-2012 (270 µg/kg) and Pegfilgrastim. Number of subjects 70, includes 34 SPI-2012 (270 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

SPI-2012 (270 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[59]

P-value

= 0.027 ^[60]

Method

ANOVA

Parameter type

Log risk ratio

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

1.07

upper limit

2.79

Variability estimate

Standard error of the mean

Notes
[59] - The analysis of variance was applied to calculate the p-value and 95% confidence interval. Unit for point estimate is x10^9/L.
[60] - There is a statistically significant difference between SPI-2012 (270µg/kg) and Pegfilgrastim in which SPI-2012 has a higher nadir compared to Pegfilgrastim.

Secondary: Depth of ANC Nadir in Cycle 3

Top of page

End point title

Depth of ANC Nadir in Cycle 3

End point description

End point type

Secondary

End point timeframe

Twenty-one (21) days of Cycle 3.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	38	32	34	36
Units: x10^9/L
median (full range (min-max))	1.9 (0.0 to 7.3)	3.4 (0.1 to 12.3)	4.1 (0.2 to 21.4)	3.5 (0.1 to 8.1)

Comparison of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

The median depth of the ANC nadir was compared between SPI-2012 (45 µg/kg) and Pegfilgrastim. Number of subjects 74, includes 38 SPI-2012 (45 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[61]

P-value

= 0.015 ^[62]

Method

ANOVA

Parameter type

Log risk ratio

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

0.89

Variability estimate

Standard error of the mean

Notes
[61] - The analysis of variance was applied to calculate the p-value and 95% confidence interval. Unit for point estimate is x10^9/L.
[62] - There is a statistically significant difference between SPI-2012 (45µg/kg) and Pegfilgrastim in which SPI-2012 has a lower nadir compared to the Pegfilgrastim arm.

Comparison of SPI-2012 (135µg/kg) vs Pegfilgrastim

Statistical analysis description

The median depth of the ANC nadir was compared between SPI-2012 (135 µg/kg) and Pegfilgrastim. Number of subjects 68, includes 32 SPI-2012 (135 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

SPI-2012 (135 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[63]

P-value

= 0.571 ^[64]

Method

ANOVA

Parameter type

Log risk ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.85

Variability estimate

Standard error of the mean

Notes
[63] - The analysis of variance was applied to calculate the p-value and 95% confidence interval. Unit for point estimate is x10^9/L.
[64] - There is no statistically significant difference between SPI-2012 (135µg/kg) and Pegfilgrastim.

Comparison of SPI-2012 (270µg/kg) vs Pegfilgrastim

Statistical analysis description

The median depth of the ANC nadir was compared between SPI-2012 (270 µg/kg) and Pegfilgrastim. Number of subjects 70, includes 34 SPI-2012 (270 μg/kg) and 36 (Pegfilgrastim).

Comparison groups

SPI-2012 (270 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[65]

P-value

= 0.066 ^[66]

Method

ANOVA

Parameter type

Log risk ratio

Point estimate

1.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

2.49

Variability estimate

Standard error of the mean

Notes
[65] - The analysis of variance was applied to calculate the p-value and 95% confidence interval. Unit for point estimate is x10^9/L.
[66] - There is no statistically significant difference between SPI-2012 (270 µg/kg) and Pegfilgrastim.

Secondary: Depth of ANC Nadir in Cycle 4

Top of page

End point title

Depth of ANC Nadir in Cycle 4

End point description

End point type

Secondary

End point timeframe

Twenty-one (21) days of Cycle 4.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	38	32	33	35
Units: x10^9/L
median (full range (min-max))	1.7 (0.0 to 9.2)	4.2 (0.1 to 11.2)	4.2 (0.4 to 11.9)	2.4 (0.1 to 6.4)

Comparison of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

The median depth of the ANC nadir was compared between SPI-2012 (45 µg/kg) and Pegfilgrastim. Number of subjects 73, includes 38 SPI-2012 (45 μg/kg) and 35 (Pegfilgrastim).

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[67]

P-value

= 0.106 ^[68]

Method

ANOVA

Parameter type

Log risk ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.1

Variability estimate

Standard error of the mean

Notes
[67] - The analysis of variance was applied to calculate the p-value and 95% confidence interval. Unit for point estimate is x10^9/L.
[68] - There is no statistically significant difference between SPI-2012 (45 µg/kg) and Pegfilgrastim.

Comparison of SPI-2012 (135µg/kg) vs Pegfilgrastim

Statistical analysis description

The median depth of the ANC nadir was compared between SPI-2012 (135 µg/kg) and Pegfilgrastim. Number of subjects 67, includes 32 SPI-2012 (135 μg/kg) and 35 (Pegfilgrastim).

Comparison groups

SPI-2012 (135 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[69]

P-value

= 0.156 ^[70]

Method

ANOVA

Parameter type

Log risk ratio

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

2.38

Variability estimate

Standard error of the mean

Notes
[69] - The analysis of variance was applied to calculate the p-value and 95% confidence interval. Unit for point estimate is x10^9/L.
[70] - There is no statistically significant difference between SPI-2012 (135 µg/kg) and Pegfilgrastim.

Comparison of SPI-2012 (270µg/kg) vs Pegfilgrastim

Statistical analysis description

The median depth of the ANC nadir was compared between SPI-2012 (270 µg/kg) and Pegfilgrastim. Number of subjects 68, includes 33 SPI-2012 (270 μg/kg) and 35 (Pegfilgrastim).

Comparison groups

SPI-2012 (270 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[71]

P-value

= 0.005 ^[72]

Method

ANOVA

Parameter type

Log risk ratio

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

2.96

Variability estimate

Standard error of the mean

Notes
[71] - The analysis of variance was applied to calculate the p-value and 95% confidence interval. Unit for point estimate is x10^9/L.
[72] - There is a statistically significant difference between SPI-2012 (270 µg/kg) and Pegfilgrastim in which SPI-2012 has a higher nadir compared to Pegfilgrastim.

Secondary: Overall febrile neutropenia across all cycles

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End point title

Overall febrile neutropenia across all cycles

End point description

Febrile neutropenia was defined as a temperature of more than 38.2°C concurrent with an ANC less than 0.5 x 106/L. Rate of FN is summarised in each cycle and overall across all cycles.

End point type

Secondary

End point timeframe

Observation timeframe of same day or +/- 1 calendar day

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	39	36	36	36
Units: number of patients	3	1	1	2

Difference of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

The overall incidence of febrile neutropenia was considered.

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[73]

P-value

= 1 ^[74]

Method

Fisher exact

Parameter type

Risk difference (RD)

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-20.2

upper limit

24.9

Variability estimate

Standard deviation

Notes
[73] - The analysis was performed using Fisher's exact test.
[74] - There is no statistically significant difference between SPI-2012 (45 µg/kg) and Pegfilgrastim.

Difference of SPI-2012 (135µg/kg) vs Pegfilgrastim

Statistical analysis description

The overall incidence of febrile neutropenia was considered.

Comparison groups

Pegfilgrastim (6 mg per PI) v SPI-2012 (135 µg/kg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[75]

P-value

= 1 ^[76]

Method

Fisher exact

Parameter type

Risk difference (RD)

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-26.7

upper limit

21.4

Variability estimate

Standard deviation

Notes
[75] - The analysis was performed using Fisher's exact test.
[76] - There is no statistically significant difference between SPI-2012 (135 µg/kg) and Pegfilgrastim.

Difference of SPI-2012 (270µg/kg) vs Pegfilgrastim

Statistical analysis description

The overall incidence of febrile neutropenia was considered.

Comparison groups

Pegfilgrastim (6 mg per PI) v SPI-2012 (270 µg/kg)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[77]

P-value

= 1 ^[78]

Method

Fisher exact

Parameter type

Risk difference (RD)

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-26.7

upper limit

21.4

Variability estimate

Standard deviation

Notes
[77] - The analysis was performed using Fisher's Exact test.
[78] - There is no statistically significant difference between SPI-2012 (270 µg/kg) and Pegfilgrastim.

Secondary: Analysis of hospitalisation rates across all cycles

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End point title

Analysis of hospitalisation rates across all cycles

End point description

All hospitalisations regardless of reason were summarised. Incidence rate of hospitalisation, number of hospitalisations and duration were calculated for each cycle and overall across all cycles. Exact 2-sided 95% I was provided for rate of hospitalisation.

End point type

Secondary

End point timeframe

Duration of hospitalisation was calculated in days for each cycle and across all cycles.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	39	36	36	36
Units: number of patients	3	3	1	5

Difference of SPI-2012 (45µg/kg) vs Pegfilgrastim

Statistical analysis description

The overall incidence of hospitalisations was considered.

Comparison groups

SPI-2012 (45 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[79]

P-value

= 0.469 ^[80]

Method

Fisher exact

Parameter type

Risk difference (RD)

Point estimate

-6.2

Confidence interval

level

95%

sides

2-sided

lower limit

-28.5

upper limit

16.9

Variability estimate

Standard deviation

Notes
[79] - The analysis was performed using Fisher's exact test.
[80] - There is no statistically significant difference between SPI-2012 (45 µg/kg) and Pegfilgrastim.

Difference of SPI-2012 (135µg/kg) vs Pegfilgrastim

Statistical analysis description

The overall incidence of hospitalisations was considered.

Comparison groups

SPI-2012 (135 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[81]

P-value

= 0.71 ^[82]

Method

Fisher exact

Parameter type

Risk difference (RD)

Point estimate

-5.6

Confidence interval

level

95%

sides

2-sided

lower limit

-29.3

upper limit

18.7

Variability estimate

Standard deviation

Notes
[81] - The analysis was performed using Fisher's exact test.
[82] - There is no statistically significant difference between SPI-2012 (135 µg/kg) and Pegfilgrastim.

Difference of SPI-2012 (270µg/kg) vs Pegfilgrastim

Statistical analysis description

The overall incidence of hospitalisations was considered.

Comparison groups

SPI-2012 (270 µg/kg) v Pegfilgrastim (6 mg per PI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[83]

P-value

= 0.199 ^[84]

Method

Fisher exact

Parameter type

Risk difference (RD)

Point estimate

-11.1

Confidence interval

level

95%

sides

2-sided

lower limit

-34.6

upper limit

13.3

Variability estimate

Standard deviation

Notes
[83] - The analysis was performed using Fisher's exact test.
[84] - There is no statistically significant difference between SPI-2012 (270 µg/kg) and Pegfilgrastim.

Secondary: SPI-2012 PK parameters - time to reach Cmax (Tmax)

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End point title

SPI-2012 PK parameters - time to reach Cmax (Tmax) ^[85]

End point description

The PK parameters were calculated based on Cycle 1 serum concentrations. PK analysis used the PK population incorporating the subset of patients who received at least one dose of SPI-2012 in Arms 1 to 3 and had sufficient number of blood samples to estimate AUC and PK parameters based on treatment arms. A test of dose proportionality was performed for PK parameters using a 2-sided test at 5% level of significance.

End point type

Secondary

End point timeframe

Blood samples for the PK assessment were collected during Cycle 1 pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, 312 and 456 hours post-dose and during Cycle 3 pre-dose and at 24, 48, 72, 144, 192, 312 and 456 hours post-dose.

Notes
[85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Analysis was descriptive and no statistical analysis was carried out.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)
Number of subjects analysed	2	4	3
Units: hour
arithmetic mean (standard deviation)	58.7 ± 23.6	9 ± 40.1	24 ± 0.1

No statistical analyses for this end point

Secondary: SPI-2012 PK parameters - observed maximum concentration post dose (Cmax)

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End point title

SPI-2012 PK parameters - observed maximum concentration post dose (Cmax) ^[86]

End point description

The PK parameters were calculated based on Cycle 1 serum concentrations. The PK parameters were calculated based on Cycle 1 serum concentrations. PK analysis used the PK population incorporating the subset of patients who received at least one dose of SPI-2012 in Arms 1 to 3 and had sufficient number of blood samples to estimate AUC and PK parameters based on treatment arms. A test of dose proportionality was performed for PK parameters using a 2-sided test at 5% level of significance.

End point type

Secondary

End point timeframe

Notes
[86] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Analysis was descriptive and no statistical analysis was carried out.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)
Number of subjects analysed	3	4	3
Units: ng/ml
arithmetic mean (standard deviation)	7 ± 6.08	247 ± 276	299 ± 329

No statistical analyses for this end point

Secondary: SPI-2012 PK parameters - Area under the serum concentration-time curve from time zero to 312 hours post-dose (AUC(0-312))

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End point title

SPI-2012 PK parameters - Area under the serum concentration-time curve from time zero to 312 hours post-dose (AUC(0-312)) ^[87]

End point description

End point type

Secondary

End point timeframe

Notes
[87] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Analysis was descriptive and no statistical analysis was carried out.

End point values	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)
Number of subjects analysed	2	3
Units: ng.hr/mL
arithmetic mean (standard deviation)	16000 ± 5850	22900 ± 25100

No statistical analyses for this end point

Secondary: SPI-2012 PK parameters - half-life (t1/2)

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End point title

SPI-2012 PK parameters - half-life (t1/2) ^[88]

End point description

End point type

Secondary

End point timeframe

Blood samples from taken from 135µg/kg and 270µg/kg SPI-2012 arm following a single subcutaneous dose in Cycle 1.

Notes
[88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Analysis was descriptive and no statistical analysis was carried out.

End point values	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)
Number of subjects analysed	2	1
Units: hour
arithmetic mean (standard deviation)	81.0 ± 88.4	31.5 ± 0.00

No statistical analyses for this end point

Secondary: Immunogenicity

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End point title

Immunogenicity

End point description

Number (or percentage) of patients who demonstrated treatment-induced formation of antidrug antibodies (ADA) in the G-CSF confirmatory assay was determined. The result was the presence of two patients out of 100 patients (2%) in the SPI-2012 arms who were negative pre-dose (C1D1) and displayed treatment-induced formation of ADA post-dose to both SPI 2012 and G-CSF. One out of 25 (4%) patients treated with pegfilgrastim, who were negative pre-dose, was positive for antibodies binding to SPI-2012 and G-CSF. These results indicate that SPI 2012 and pegfilgrastim are minimally immunogenic.

End point type

Secondary

End point timeframe

The immunogenicity data was collected on Day -1 and at the end of study visit of each cycle.

End point values	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg per PI)
Number of subjects analysed	35	35	30	25
Units: Number of patients	0	0	2	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From consent of patient until the first dose of study treatment was to be recorded on the AE CRF page(s). All AEs occurring up to 30 days after the last dose of study drugs were also recorded in the CRF.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

13.1

Reporting group title

SPI-2012 (45 µg/kg)

Reporting group description

Reporting group title

SPI-2012 (135 µg/kg)

Reporting group description

Reporting group title

SPI-2012 (270 µg/kg)

Reporting group description

Reporting group title

Pegfilgrastim (6 mg)

Reporting group description

Serious adverse events	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg)
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 39 (12.82%)	4 / 37 (10.81%)	2 / 36 (5.56%)	8 / 36 (22.22%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Injury, poisoning and procedural complications
Road traffic accident
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina pectoris
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Febrile neutropenia
subjects affected / exposed	2 / 39 (5.13%)	1 / 37 (2.70%)	1 / 36 (2.78%)	1 / 36 (2.78%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	0 / 39 (0.00%)	1 / 37 (2.70%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	2 / 36 (5.56%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Vaginal haemorrhage
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure acute
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bacteraemia
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	1 / 36 (2.78%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis viral
subjects affected / exposed	0 / 39 (0.00%)	1 / 37 (2.70%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 39 (0.00%)	1 / 37 (2.70%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	SPI-2012 (45 µg/kg)	SPI-2012 (135 µg/kg)	SPI-2012 (270 µg/kg)	Pegfilgrastim (6 mg)
Total subjects affected by non serious adverse events
subjects affected / exposed	36 / 39 (92.31%)	33 / 37 (89.19%)	33 / 36 (91.67%)	35 / 36 (97.22%)
Vascular disorders
Flushing
subjects affected / exposed	4 / 39 (10.26%)	3 / 37 (8.11%)	5 / 36 (13.89%)	6 / 36 (16.67%)
occurrences all number	6	5	11	15
Hot flush
subjects affected / exposed	1 / 39 (2.56%)	3 / 37 (8.11%)	1 / 36 (2.78%)	5 / 36 (13.89%)
occurrences all number	2	3	1	9
Hypertension
subjects affected / exposed	2 / 39 (5.13%)	1 / 37 (2.70%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences all number	3	1	0	0
Lymphoedema
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	1 / 36 (2.78%)	2 / 36 (5.56%)
occurrences all number	1	0	1	2
Surgical and medical procedures
Catheter removal
subjects affected / exposed	2 / 39 (5.13%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences all number	2	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	5 / 39 (12.82%)	2 / 37 (5.41%)	5 / 36 (13.89%)	8 / 36 (22.22%)
occurrences all number	6	2	5	12
Chest discomfort
subjects affected / exposed	3 / 39 (7.69%)	0 / 37 (0.00%)	1 / 36 (2.78%)	2 / 36 (5.56%)
occurrences all number	3	0	1	3
Chest pain
subjects affected / exposed	3 / 39 (7.69%)	1 / 37 (2.70%)	2 / 36 (5.56%)	3 / 36 (8.33%)
occurrences all number	3	1	2	3
Chills
subjects affected / exposed	2 / 39 (5.13%)	0 / 37 (0.00%)	1 / 36 (2.78%)	1 / 36 (2.78%)
occurrences all number	2	0	1	1
Device occlusion
subjects affected / exposed	2 / 39 (5.13%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences all number	3	0	0	0
Fatigue
subjects affected / exposed	24 / 39 (61.54%)	11 / 37 (29.73%)	19 / 36 (52.78%)	20 / 36 (55.56%)
occurrences all number	52	16	42	35
Influenza like illness
subjects affected / exposed	2 / 39 (5.13%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)
occurrences all number	3	0	0	1
Mucosal inflammation
subjects affected / exposed	3 / 39 (7.69%)	2 / 37 (5.41%)	1 / 36 (2.78%)	2 / 36 (5.56%)
occurrences all number	3	3	1	2
Oedema peripheral
subjects affected / exposed	9 / 39 (23.08%)	4 / 37 (10.81%)	7 / 36 (19.44%)	5 / 36 (13.89%)
occurrences all number	11	5	8	7
Pain
subjects affected / exposed	2 / 39 (5.13%)	2 / 37 (5.41%)	2 / 36 (5.56%)	2 / 36 (5.56%)
occurrences all number	5	6	2	3
Pyrexia
subjects affected / exposed	4 / 39 (10.26%)	3 / 37 (8.11%)	4 / 36 (11.11%)	6 / 36 (16.67%)
occurrences all number	4	3	4	6
Hypersensitivity
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	2 / 36 (5.56%)	0 / 36 (0.00%)
occurrences all number	0	0	2	0
Seasonal allergy
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	2 / 36 (5.56%)	0 / 36 (0.00%)
occurrences all number	0	0	2	0
Device related infection
subjects affected / exposed	2 / 39 (5.13%)	1 / 37 (2.70%)	0 / 36 (0.00%)	1 / 36 (2.78%)
occurrences all number	3	1	0	1
Nasopharyngitis
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	2 / 36 (5.56%)	2 / 36 (5.56%)
occurrences all number	1	0	2	2
Upper respiratory tract infection
subjects affected / exposed	2 / 39 (5.13%)	1 / 37 (2.70%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences all number	2	1	0	0
Urinary tract infection
subjects affected / exposed	2 / 39 (5.13%)	1 / 37 (2.70%)	1 / 36 (2.78%)	2 / 36 (5.56%)
occurrences all number	3	1	2	2
Vaginal infection
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	2 / 36 (5.56%)	0 / 36 (0.00%)
occurrences all number	0	0	5	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	7 / 39 (17.95%)	2 / 37 (5.41%)	4 / 36 (11.11%)	6 / 36 (16.67%)
occurrences all number	7	2	4	9
Dyspnoea
subjects affected / exposed	6 / 39 (15.38%)	2 / 37 (5.41%)	4 / 36 (11.11%)	3 / 36 (8.33%)
occurrences all number	8	2	5	3
Epistaxis
subjects affected / exposed	8 / 39 (20.51%)	3 / 37 (8.11%)	0 / 36 (0.00%)	1 / 36 (2.78%)
occurrences all number	8	3	0	1
Oropharyngeal pain
subjects affected / exposed	2 / 39 (5.13%)	2 / 37 (5.41%)	2 / 36 (5.56%)	4 / 36 (11.11%)
occurrences all number	2	2	2	5
Rhinorrhoea
subjects affected / exposed	1 / 39 (2.56%)	2 / 37 (5.41%)	2 / 36 (5.56%)	2 / 36 (5.56%)
occurrences all number	1	2	2	2
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 39 (0.00%)	1 / 37 (2.70%)	1 / 36 (2.78%)	2 / 36 (5.56%)
occurrences all number	0	1	1	2
Insomnia
subjects affected / exposed	3 / 39 (7.69%)	5 / 37 (13.51%)	5 / 36 (13.89%)	11 / 36 (30.56%)
occurrences all number	6	6	5	17
Investigations
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 39 (0.00%)	1 / 37 (2.70%)	2 / 36 (5.56%)	0 / 36 (0.00%)
occurrences all number	0	1	3	0
Blood creatinine increased
subjects affected / exposed	2 / 39 (5.13%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences all number	2	0	0	0
Lymphocyte count decreased
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	2 / 36 (5.56%)	0 / 36 (0.00%)
occurrences all number	14	0	6	0
Neutrophil count decreased
subjects affected / exposed	13 / 39 (33.33%)	3 / 37 (8.11%)	8 / 36 (22.22%)	5 / 36 (13.89%)
occurrences all number	31	7	13	12
Platelet count decreased
subjects affected / exposed	0 / 39 (0.00%)	1 / 37 (2.70%)	6 / 36 (16.67%)	0 / 36 (0.00%)
occurrences all number	0	1	16	0
White blood cell count decreased
subjects affected / exposed	4 / 39 (10.26%)	0 / 37 (0.00%)	2 / 36 (5.56%)	1 / 36 (2.78%)
occurrences all number	14	0	10	4
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	2 / 39 (5.13%)	0 / 37 (0.00%)	0 / 36 (0.00%)	2 / 36 (5.56%)
occurrences all number	3	0	0	2
Infusion related reaction
subjects affected / exposed	2 / 39 (5.13%)	4 / 37 (10.81%)	1 / 36 (2.78%)	1 / 36 (2.78%)
occurrences all number	3	5	2	1
Cardiac disorders
Palpitations
subjects affected / exposed	2 / 39 (5.13%)	0 / 37 (0.00%)	1 / 36 (2.78%)	2 / 36 (5.56%)
occurrences all number	2	0	1	2
Tachycardia
subjects affected / exposed	0 / 39 (0.00%)	3 / 37 (8.11%)	1 / 36 (2.78%)	1 / 36 (2.78%)
occurrences all number	0	3	1	1
Nervous system disorders
Dizziness
subjects affected / exposed	4 / 39 (10.26%)	0 / 37 (0.00%)	4 / 36 (11.11%)	2 / 36 (5.56%)
occurrences all number	7	0	5	2
Dysgeusia
subjects affected / exposed	10 / 39 (25.64%)	2 / 37 (5.41%)	4 / 36 (11.11%)	4 / 36 (11.11%)
occurrences all number	13	2	6	7
Headache
subjects affected / exposed	12 / 39 (30.77%)	5 / 37 (13.51%)	8 / 36 (22.22%)	9 / 36 (25.00%)
occurrences all number	17	5	16	18
Hypoaesthesia
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	0 / 36 (0.00%)	2 / 36 (5.56%)
occurrences all number	2	0	0	3
Lethargy
subjects affected / exposed	2 / 39 (5.13%)	1 / 37 (2.70%)	1 / 36 (2.78%)	2 / 36 (5.56%)
occurrences all number	3	1	1	2
Memory impairment
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	2 / 36 (5.56%)
occurrences all number	0	0	0	2
Neuropathy peripheral
subjects affected / exposed	4 / 39 (10.26%)	2 / 37 (5.41%)	2 / 36 (5.56%)	5 / 36 (13.89%)
occurrences all number	5	2	2	5
Paraesthesia
subjects affected / exposed	2 / 39 (5.13%)	0 / 37 (0.00%)	2 / 36 (5.56%)	1 / 36 (2.78%)
occurrences all number	2	0	2	3
Peripheral sensory neuropathy
subjects affected / exposed	3 / 39 (7.69%)	1 / 37 (2.70%)	2 / 36 (5.56%)	1 / 36 (2.78%)
occurrences all number	5	2	3	3
Polyneuropathy
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	2 / 36 (5.56%)	0 / 36 (0.00%)
occurrences all number	0	0	2	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	10 / 39 (25.64%)	2 / 37 (5.41%)	5 / 36 (13.89%)	6 / 36 (16.67%)
occurrences all number	26	7	27	11
Febrile neutropenia
subjects affected / exposed	1 / 39 (2.56%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)
occurrences all number	2	0	0	1
Leukocytosis
subjects affected / exposed	2 / 39 (5.13%)	4 / 37 (10.81%)	7 / 36 (19.44%)	2 / 36 (5.56%)
occurrences all number	9	9	18	3
Leukopenia
subjects affected / exposed	5 / 39 (12.82%)	2 / 37 (5.41%)	1 / 36 (2.78%)	1 / 36 (2.78%)
occurrences all number	10	5	1	3
Neutropenia
subjects affected / exposed	11 / 39 (28.21%)	2 / 37 (5.41%)	2 / 36 (5.56%)	5 / 36 (13.89%)
occurrences all number	43	3	3	16
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	3 / 39 (7.69%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences all number	3	0	0	0
Eye disorders
Blepharospasm
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	2 / 36 (5.56%)	0 / 36 (0.00%)
occurrences all number	0	0	3	0
Lacrimation increased
subjects affected / exposed	3 / 39 (7.69%)	4 / 37 (10.81%)	2 / 36 (5.56%)	2 / 36 (5.56%)
occurrences all number	3	4	2	3
Vision blurred
subjects affected / exposed	2 / 39 (5.13%)	0 / 37 (0.00%)	1 / 36 (2.78%)	1 / 36 (2.78%)
occurrences all number	2	0	2	1
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	2 / 39 (5.13%)	1 / 37 (2.70%)	1 / 36 (2.78%)	1 / 36 (2.78%)
occurrences all number	2	1	2	2
Abdominal pain
subjects affected / exposed	3 / 39 (7.69%)	3 / 37 (8.11%)	2 / 36 (5.56%)	3 / 36 (8.33%)
occurrences all number	10	3	2	3
Abdominal pain upper
subjects affected / exposed	3 / 39 (7.69%)	1 / 37 (2.70%)	0 / 36 (0.00%)	1 / 36 (2.78%)
occurrences all number	4	1	0	2
Constipation
subjects affected / exposed	7 / 39 (17.95%)	7 / 37 (18.92%)	11 / 36 (30.56%)	7 / 36 (19.44%)
occurrences all number	13	8	22	11
Diarrhoea
subjects affected / exposed	17 / 39 (43.59%)	7 / 37 (18.92%)	14 / 36 (38.89%)	15 / 36 (41.67%)
occurrences all number	35	14	20	16
Dry mouth
subjects affected / exposed	5 / 39 (12.82%)	1 / 37 (2.70%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences all number	5	1	0	0
Dyspepsia
subjects affected / exposed	3 / 39 (7.69%)	3 / 37 (8.11%)	8 / 36 (22.22%)	2 / 36 (5.56%)
occurrences all number	3	4	9	2
Dysphagia
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	2 / 36 (5.56%)	0 / 36 (0.00%)
occurrences all number	0	0	2	0
Nausea
subjects affected / exposed	19 / 39 (48.72%)	12 / 37 (32.43%)	15 / 36 (41.67%)	16 / 36 (44.44%)
occurrences all number	33	17	30	27
Stomatitis
subjects affected / exposed	8 / 39 (20.51%)	3 / 37 (8.11%)	5 / 36 (13.89%)	3 / 36 (8.33%)
occurrences all number	12	3	9	3
Vomiting
subjects affected / exposed	5 / 39 (12.82%)	5 / 37 (13.51%)	1 / 36 (2.78%)	5 / 36 (13.89%)
occurrences all number	8	5	1	5
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	21 / 39 (53.85%)	18 / 37 (48.65%)	12 / 36 (33.33%)	13 / 36 (36.11%)
occurrences all number	28	25	16	19
Dermatitis
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	2 / 36 (5.56%)	0 / 36 (0.00%)
occurrences all number	0	0	2	0
Dry skin
subjects affected / exposed	4 / 39 (10.26%)	0 / 37 (0.00%)	2 / 36 (5.56%)	1 / 36 (2.78%)
occurrences all number	5	0	2	2
Erythema
subjects affected / exposed	1 / 39 (2.56%)	2 / 37 (5.41%)	1 / 36 (2.78%)	1 / 36 (2.78%)
occurrences all number	1	2	1	1
Nail discolouration
subjects affected / exposed	2 / 39 (5.13%)	0 / 37 (0.00%)	1 / 36 (2.78%)	3 / 36 (8.33%)
occurrences all number	2	0	1	3
Nail ridging
subjects affected / exposed	2 / 39 (5.13%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)
occurrences all number	2	0	0	1
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	1 / 39 (2.56%)	3 / 37 (8.11%)	0 / 36 (0.00%)	2 / 36 (5.56%)
occurrences all number	1	3	0	2
Pruritus
subjects affected / exposed	4 / 39 (10.26%)	3 / 37 (8.11%)	2 / 36 (5.56%)	4 / 36 (11.11%)
occurrences all number	4	4	2	4
Rash
subjects affected / exposed	9 / 39 (23.08%)	4 / 37 (10.81%)	8 / 36 (22.22%)	5 / 36 (13.89%)
occurrences all number	16	10	8	5
Rash maculo-papular
subjects affected / exposed	1 / 39 (2.56%)	1 / 37 (2.70%)	1 / 36 (2.78%)	2 / 36 (5.56%)
occurrences all number	1	1	1	2
Skin exfoliation
subjects affected / exposed	3 / 39 (7.69%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences all number	6	0	0	0
Urticaria
subjects affected / exposed	2 / 39 (5.13%)	2 / 37 (5.41%)	2 / 36 (5.56%)	3 / 36 (8.33%)
occurrences all number	2	4	2	3
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 39 (2.56%)	1 / 37 (2.70%)	2 / 36 (5.56%)	1 / 36 (2.78%)
occurrences all number	1	1	5	2
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	5 / 39 (12.82%)	7 / 37 (18.92%)	6 / 36 (16.67%)	7 / 36 (19.44%)
occurrences all number	15	11	10	11
Back pain
subjects affected / exposed	8 / 39 (20.51%)	6 / 37 (16.22%)	5 / 36 (13.89%)	4 / 36 (11.11%)
occurrences all number	14	6	6	12
Bone pain
subjects affected / exposed	9 / 39 (23.08%)	10 / 37 (27.03%)	12 / 36 (33.33%)	13 / 36 (36.11%)
occurrences all number	19	14	18	15
Muscular weakness
subjects affected / exposed	1 / 39 (2.56%)	1 / 37 (2.70%)	2 / 36 (5.56%)	0 / 36 (0.00%)
occurrences all number	1	1	2	0
Musculoskeletal chest pain
subjects affected / exposed	2 / 39 (5.13%)	0 / 37 (0.00%)	1 / 36 (2.78%)	0 / 36 (0.00%)
occurrences all number	2	0	1	0
Musculoskeletal pain
subjects affected / exposed	2 / 39 (5.13%)	2 / 37 (5.41%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences all number	2	2	0	0
Myalgia
subjects affected / exposed	8 / 39 (20.51%)	7 / 37 (18.92%)	9 / 36 (25.00%)	7 / 36 (19.44%)
occurrences all number	12	10	12	12
Neck pain
subjects affected / exposed	3 / 39 (7.69%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences all number	5	0	0	0
Osteopenia
subjects affected / exposed	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	2 / 36 (5.56%)
occurrences all number	0	0	0	2
Pain in extremity
subjects affected / exposed	4 / 39 (10.26%)	2 / 37 (5.41%)	4 / 36 (11.11%)	1 / 36 (2.78%)
occurrences all number	4	3	4	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	6 / 39 (15.38%)	2 / 37 (5.41%)	3 / 36 (8.33%)	2 / 36 (5.56%)
occurrences all number	7	2	3	2
Dehydration
subjects affected / exposed	4 / 39 (10.26%)	1 / 37 (2.70%)	0 / 36 (0.00%)	1 / 36 (2.78%)
occurrences all number	4	1	0	1
Hypertriglyceridaemia
subjects affected / exposed	2 / 39 (5.13%)	1 / 37 (2.70%)	0 / 36 (0.00%)	0 / 36 (0.00%)
occurrences all number	4	2	0	0
Hypokalaemia
subjects affected / exposed	4 / 39 (10.26%)	0 / 37 (0.00%)	1 / 36 (2.78%)	1 / 36 (2.78%)
occurrences all number	4	0	2	1
Hyponatraemia
subjects affected / exposed	3 / 39 (7.69%)	0 / 37 (0.00%)	1 / 36 (2.78%)	1 / 36 (2.78%)
occurrences all number	3	0	2	1

More information

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Were there any global substantial amendments to the protocol? Yes

10 Jul 2013

Increase in the number of study centres from 20 to 55 centres. Some Inclusion criteria were modified to expand inclusion and some Exclusion criteria were modified for clarity.

03 Feb 2014

Addition of a pharmacokinetic subset of patients.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

SD was not calculated for the PK parameter of half-life in the 270 µg/kg cohort. The integer '0' and 'arbitary' median and ranges for median ANC endpoint were used to pass validation. Analysis patterns were graphically demonstrated.

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Clinical trials

Clinical Trial Results: Phase 2, Open-Label, Dose-Ranging Study of HM10460A or Pegfilgrastim use for the Management of Neutropenia in Patients with Breast Cancer who are Candidates for Adjuvant and Neoadjuvant Chemotherapy with the Docetaxel + Cyclophosphamide (TC) Regimen.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Duration of severe neutropenia (DSN) in Cycle 1

Primary: Duration of severe neutropenia (DSN) in Cycle 1

Secondary: Duration of severe neutropenia (DSN) in Cycle 2

Secondary: Duration of severe neutropenia (DSN) in Cycle 2

Secondary: Duration of severe neutropenia (DSN) in Cycle 3

Secondary: Duration of severe neutropenia (DSN) in Cycle 3

Secondary: Duration of severe neutropenia (DSN) in Cycle 4

Secondary: Duration of severe neutropenia (DSN) in Cycle 4

Secondary: Time to ANC recovery in Cycle 1

Secondary: Time to ANC recovery in Cycle 1

Secondary: Time to ANC recovery in Cycle 2

Secondary: Time to ANC recovery in Cycle 2

Secondary: Time to ANC recovery in Cycle 3

Secondary: Time to ANC recovery in Cycle 3

Secondary: Time to ANC recovery in Cycle 4

Secondary: Time to ANC recovery in Cycle 4

Secondary: Depth of ANC Nadir in Cycle 1

Secondary: Depth of ANC Nadir in Cycle 1

Secondary: Depth of ANC Nadir in Cycle 2

Secondary: Depth of ANC Nadir in Cycle 2

Secondary: Depth of ANC Nadir in Cycle 3

Secondary: Depth of ANC Nadir in Cycle 3

Secondary: Depth of ANC Nadir in Cycle 4

Secondary: Depth of ANC Nadir in Cycle 4

Secondary: Overall febrile neutropenia across all cycles

Secondary: Overall febrile neutropenia across all cycles

Secondary: Analysis of hospitalisation rates across all cycles

Secondary: Analysis of hospitalisation rates across all cycles

Secondary: SPI-2012 PK parameters - time to reach Cmax (Tmax)

Secondary: SPI-2012 PK parameters - time to reach Cmax (Tmax)

Secondary: SPI-2012 PK parameters - observed maximum concentration post dose (Cmax)

Secondary: SPI-2012 PK parameters - observed maximum concentration post dose (Cmax)

Secondary: SPI-2012 PK parameters - Area under the serum concentration-time curve from time zero to 312 hours post-dose (AUC(0-312))

Secondary: SPI-2012 PK parameters - Area under the serum concentration-time curve from time zero to 312 hours post-dose (AUC(0-312))

Secondary: SPI-2012 PK parameters - half-life (t1/2)

Secondary: SPI-2012 PK parameters - half-life (t1/2)

Secondary: Immunogenicity

Secondary: Immunogenicity

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Phase 2, Open-Label, Dose-Ranging Study of HM10460A or Pegfilgrastim use for the Management of Neutropenia in Patients with Breast Cancer who are Candidates for Adjuvant and Neoadjuvant Chemotherapy with the Docetaxel + Cyclophosphamide (TC) Regimen.