Trial Outcomes & Findings for Comparative Immunogenicity Study of Multiple Doses of Proposed Pegfilgrastim Biosimilar, INTP5 of Intas Pharmaceuticals Ltd., India Against Neulasta of Amgen Inc., USA in Healthy, Adult Human Subjects. (NCT NCT04015232)
NCT ID: NCT04015232
Last Updated: 2019-10-04
Results Overview
Immunogenicity (anti-drug antibody; ADA) data is presented for all subjects' samples collected and a descriptive analysis is provided for immunogenicity (ADA) data. Percentage incidence within + 10% of the expected ADA positivity incidence of Test (6% ADA in Test is anticipated from literature) is not considered clinically significant. Evaluation of immunogenicity is carried out in a tiered fashion: 1. Screening assay to assess if samples were positive or negative for anti-PegG-CSF. 2. Confirmatory assays for samples that were positive in the screening assay. The confirmatory assays assessed if antibodies were specific for INTP5, Neulasta, PEG and/or filgrastim. 3. Titer assay was performed to determine titer of the anti-PEG-GCSF antibody samples. 4. Neutralizing antibody (NAb) assay for those samples that were positive in the confirmatory assays to assess the neutralizing capability of the antibody to inhibit pegfilgrastim activity.
COMPLETED
PHASE1
200 participants
Samples (8 mL each) were withdrawn at screening, at pre-dose and at 336 (D-15, Week 2), 504 (D-22, Week 3, within 60 minutes before 2nd dose), 840 (D-36, Week 5), 1176 (D-50, Week 7), 1680 (D-71, Week 10) and 2016 (D-85, Week 12) hours after first dose.
2019-10-04
Participant Flow
Participant milestones
| Measure |
INTP5 Biosimilar Product
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|
|
Overall Study
STARTED
|
100
|
100
|
|
Overall Study
COMPLETED
|
89
|
93
|
|
Overall Study
NOT COMPLETED
|
11
|
7
|
Reasons for withdrawal
| Measure |
INTP5 Biosimilar Product
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
7
|
4
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Medical Grounds
|
3
|
3
|
Baseline Characteristics
Comparative Immunogenicity Study of Multiple Doses of Proposed Pegfilgrastim Biosimilar, INTP5 of Intas Pharmaceuticals Ltd., India Against Neulasta of Amgen Inc., USA in Healthy, Adult Human Subjects.
Baseline characteristics by cohort
| Measure |
INTP5 Biosimilar Product
n=100 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=100 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
Total
n=200 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
31.5 years
STANDARD_DEVIATION 6.82 • n=5 Participants
|
34.3 years
STANDARD_DEVIATION 6.05 • n=7 Participants
|
32.9 years
STANDARD_DEVIATION 6.58 • n=5 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
60 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
120 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
100 Participants
n=5 Participants
|
100 Participants
n=7 Participants
|
200 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
India
|
100 Participants
n=5 Participants
|
100 Participants
n=7 Participants
|
200 Participants
n=5 Participants
|
|
Height
|
160.2 cm
STANDARD_DEVIATION 8.48 • n=5 Participants
|
160.1 cm
STANDARD_DEVIATION 8.68 • n=7 Participants
|
160.2 cm
STANDARD_DEVIATION 8.56 • n=5 Participants
|
|
Weight
|
61.3 kg
STANDARD_DEVIATION 8.31 • n=5 Participants
|
62.6 kg
STANDARD_DEVIATION 7.49 • n=7 Participants
|
61.9 kg
STANDARD_DEVIATION 7.92 • n=5 Participants
|
|
BMI
|
23.95 kg/m^2
STANDARD_DEVIATION 3.069 • n=5 Participants
|
24.51 kg/m^2
STANDARD_DEVIATION 3.266 • n=7 Participants
|
24.23 kg/m^2
STANDARD_DEVIATION 3.173 • n=5 Participants
|
PRIMARY outcome
Timeframe: Samples (8 mL each) were withdrawn at screening, at pre-dose and at 336 (D-15, Week 2), 504 (D-22, Week 3, within 60 minutes before 2nd dose), 840 (D-36, Week 5), 1176 (D-50, Week 7), 1680 (D-71, Week 10) and 2016 (D-85, Week 12) hours after first dose.Immunogenicity (anti-drug antibody; ADA) data is presented for all subjects' samples collected and a descriptive analysis is provided for immunogenicity (ADA) data. Percentage incidence within + 10% of the expected ADA positivity incidence of Test (6% ADA in Test is anticipated from literature) is not considered clinically significant. Evaluation of immunogenicity is carried out in a tiered fashion: 1. Screening assay to assess if samples were positive or negative for anti-PegG-CSF. 2. Confirmatory assays for samples that were positive in the screening assay. The confirmatory assays assessed if antibodies were specific for INTP5, Neulasta, PEG and/or filgrastim. 3. Titer assay was performed to determine titer of the anti-PEG-GCSF antibody samples. 4. Neutralizing antibody (NAb) assay for those samples that were positive in the confirmatory assays to assess the neutralizing capability of the antibody to inhibit pegfilgrastim activity.
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=94 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=100 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies.
Positive for Anti-Drug-Antibody
|
10 Participants
|
9 Participants
|
—
|
—
|
|
Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies.
Positive in Neutralizing Anti-Drug-Antibody
|
0 Participants
|
0 Participants
|
—
|
—
|
|
Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies.
No Anit-Drug Antibody Confirmed Positive Results
|
84 Participants
|
91 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta.
Pharmacokinetic (PK) properties of the test and reference formulations were assessed by measuring serum Pegfilgrastim concentration. Maximum measured serum concentration, calculated from the serum concentration vs. time profile of the individual subjects.
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=10 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=10 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PK Endpoints: Pegfilgrastim C[Max]
|
483.230 ng/mL
Standard Deviation 175.1787
|
346.018 ng/mL
Standard Deviation 150.4879
|
368.569 ng/mL
Standard Deviation 223.3380
|
371.778 ng/mL
Standard Deviation 263.4440
|
SECONDARY outcome
Timeframe: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
Area under the serum concentration vs. time curve, calculated by linear trapezoidal rule from measured data points from the time zero to the time of last quantified concentration.
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=10 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=10 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PK Endpoints: Pegfilgrastim AUC[0-t]
|
22417.938 ng.h/mL
Standard Deviation 9922.2648
|
13640.695 ng.h/mL
Standard Deviation 6709.2752
|
16610.870 ng.h/mL
Standard Deviation 11255.1296
|
15255.327 ng.h/mL
Standard Deviation 11050.7580
|
SECONDARY outcome
Timeframe: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
Area under the serum concentration versus time curve from time zero to infinity. Where AUC\[0-infinity\]= AUC\[0-t\] + Ct/lambda-z, Ct is the last measurable concentration and lamda-z is the terminal rate constant. AUC\[0-infinity\] is the sum of measurable and extrapolated parts.
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=10 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=10 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PK Endpoints: Pegfilgrastim AUC[0-∞]
|
22436.497 ng.h/mL
Standard Deviation 9922.4383
|
13637.403 ng.h/mL
Standard Deviation 6699.9736
|
16630.861 ng.h/mL
Standard Deviation 11253.7406
|
15280.376 ng.h/mL
Standard Deviation 11058.1142
|
SECONDARY outcome
Timeframe: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
The time of observing the peak concentration, calculated from the serum concentration vs. time profile of the individual subjects.
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=10 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=10 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PK Endpoints: Pegfilgrastim T[Max]
|
22.405 h
Standard Deviation 3.3758
|
20.800 h
Standard Deviation 5.5936
|
22.226 h
Standard Deviation 3.5298
|
23.111 h
Standard Deviation 2.6667
|
SECONDARY outcome
Timeframe: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
Terminal rate constant: First order rate constant associated with the terminal (log-linear) portion of the curve. This was estimated via linear regression of time vs. log concentration. This parameter was calculated by linear least squares regression analysis using last three or more nonzero plasma concentration values.
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=10 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=10 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PK Endpoints: Pegfilgrastim λz (Lambda-z)
|
0.021 1/h
Standard Deviation 0.0071
|
0.025 1/h
Standard Deviation 0.0142
|
0.022 1/h
Standard Deviation 0.0058
|
0.019 1/h
Standard Deviation 0.0074
|
SECONDARY outcome
Timeframe: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
Goodness of fit statistic for the terminal phase, adjusted for the number of points used in the estimation of λz (lambda-z). R\^2 is the coefficient of determination and can range from 0 to 1, with higher values indicating greater predictability.
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=10 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=10 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PK Endpoints: Pegfilgrastim R^2 Adjusted
|
0.968 Coefficient of Determination
Standard Deviation 0.0379
|
0.876 Coefficient of Determination
Standard Deviation 0.133
|
0.974 Coefficient of Determination
Standard Deviation 0.0245
|
0.879 Coefficient of Determination
Standard Deviation 0.2339
|
SECONDARY outcome
Timeframe: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
The residual area in percentage determined by the formula, \[(AUC\[0-infinity\]-AUC\[0-t\])/AUC\[0-infinity\]\] x 100.
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=10 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=10 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PK Endpoints: Pegfilgrastim AUC[_%Extrap_Obs]
|
0.115 percentage of AUC
Standard Deviation 0.1106
|
0.644 percentage of AUC
Standard Deviation 1.4428
|
0.230 percentage of AUC
Standard Deviation 0.2672
|
0.266 percentage of AUC
Standard Deviation 0.2664
|
SECONDARY outcome
Timeframe: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
The terminal half-life calculated using the formula 0.693/(lambda-z)
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=10 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=10 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=9 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PK Endpoints: Pegfilgrastim t[1/2]
|
36.721 h
Standard Deviation 11.0052
|
36.612 h
Standard Deviation 19.6215
|
34.172 h
Standard Deviation 8.8669
|
40.616 h
Standard Deviation 14.6054
|
SECONDARY outcome
Timeframe: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
Maximum measured absolute neutrophil count (ANC).
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=89 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=89 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=93 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=93 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PD Endpoints for Baseline Non-adjusted ANC: E[Max]
ADA-NEGATIVE
|
40.72 x10^3cells/uL
Standard Deviation 10.862
|
44.63 x10^3cells/uL
Standard Deviation 11.077
|
38.34 x10^3cells/uL
Standard Deviation 9.925
|
40.62 x10^3cells/uL
Standard Deviation 8.963
|
|
PD Endpoints for Baseline Non-adjusted ANC: E[Max]
ADA-POSITIVE
|
42.89 x10^3cells/uL
Standard Deviation 10.512
|
46.53 x10^3cells/uL
Standard Deviation 9.093
|
38.38 x10^3cells/uL
Standard Deviation 8.211
|
44.96 x10^3cells/uL
Standard Deviation 16.409
|
SECONDARY outcome
Timeframe: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
Area under the ANC versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=89 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=89 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=93 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=93 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PD Endpoints for Baseline Non-adjusted ANC: T[Max]
ADA-NEGATIVE
|
64.710 h
Standard Deviation 11.1076
|
59.587 h
Standard Deviation 14.9170
|
63.182 h
Standard Deviation 15.8763
|
64.637 h
Standard Deviation 20.5772
|
|
PD Endpoints for Baseline Non-adjusted ANC: T[Max]
ADA-POSITIVE
|
72.003 h
Standard Deviation 0.0072
|
67.453 h
Standard Deviation 15.7091
|
64.002 h
Standard Deviation 12.0014
|
61.461 h
Standard Deviation 29.9401
|
SECONDARY outcome
Timeframe: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.Population: Table breaks participants into ADA(-) or ADA(+), totaling the overall number of participants by arm. 5 Subjects having three consecutive missing samples in elimination phase were excluded from the analysis of AUEC0-t reducing the total participants to 88 for INTP5 Dose 1, 88 for INTP5 Dose 2, 92 for Neulasta Dose 1, and 91 for Neulasta Dose 2.
Time to reach the maximum measured absolute neutrophil count (ANC)
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=88 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=88 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=92 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=91 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t]
ADA-NEGATIVE
|
7107.14 h*ng/mL
Standard Deviation 1481.971
|
7929.25 h*ng/mL
Standard Deviation 1561.246
|
6718.70 h*ng/mL
Standard Deviation 1361.957
|
7359.09 h*ng/mL
Standard Deviation 1455.570
|
|
PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t]
ADA-POSITIVE
|
7286.53 h*ng/mL
Standard Deviation 1744.737
|
8539.99 h*ng/mL
Standard Deviation 1522.935
|
6846.77 h*ng/mL
Standard Deviation 763.675
|
7761.65 h*ng/mL
Standard Deviation 1658.478
|
SECONDARY outcome
Timeframe: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
Maximum measured absolute neutrophil count (ANC).
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=88 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=88 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=91 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=89 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PD Endpoints for Baseline Adjusted ANC: E[Max]
ADA-NEGATIVE
|
36.50 x10^3cells/uL
Standard Deviation 10.458
|
40.80 x10^3cells/uL
Standard Deviation 11.038
|
33.35 x10^3cells/uL
Standard Deviation 9.189
|
36.56 x10^3cells/uL
Standard Deviation 8.755
|
|
PD Endpoints for Baseline Adjusted ANC: E[Max]
ADA-POSITIVE
|
38.37 x10^3cells/uL
Standard Deviation 9.548
|
42.50 x10^3cells/uL
Standard Deviation 10.061
|
34.18 x10^3cells/uL
Standard Deviation 8.503
|
40.76 x10^3cells/uL
Standard Deviation 17.170
|
SECONDARY outcome
Timeframe: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=87 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=87 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=90 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=89 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PD Endpoints for Baseline Adjusted ANC: AUEC[0-t]
ADA-NEGATIVE
|
4920.26 x10^3cells*h/uL
Standard Deviation 1339.674
|
5992.49 x10^3cells*h/uL
Standard Deviation 1555.062
|
4389.55 x10^3cells*h/uL
Standard Deviation 1140.655
|
5441.01 x10^3cells*h/uL
Standard Deviation 1478.241
|
|
PD Endpoints for Baseline Adjusted ANC: AUEC[0-t]
ADA-POSITIVE
|
4967.86 x10^3cells*h/uL
Standard Deviation 1229.792
|
6539.58 x10^3cells*h/uL
Standard Deviation 2202.473
|
4578.32 x10^3cells*h/uL
Standard Deviation 1200.125
|
5676.92 x10^3cells*h/uL
Standard Deviation 1991.456
|
SECONDARY outcome
Timeframe: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
Time to reach the maximum measured absolute neutrophil count (ANC)
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=88 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=88 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=91 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=91 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PD Endpoints for Baseline Adjusted ANC: T[Max]
ADA-NEGATIVE
|
64.617 h
Standard Deviation 11.1482
|
59.735 h
Standard Deviation 14.9546
|
65.553 h
Standard Deviation 15.8887
|
65.043 h
Standard Deviation 20.6610
|
|
PD Endpoints for Baseline Adjusted ANC: T[Max]
ADA-POSITIVE
|
72.003 h
Standard Deviation 0.0072
|
67.453 h
Standard Deviation 15.7091
|
64.002 h
Standard Deviation 12.0014
|
61.461 h
Standard Deviation 29.9401
|
SECONDARY outcome
Timeframe: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
First order rate constant associated with the terminal (log-linear) portion of the curve. This was estimated via linear regression of time vs. log concentration. This parameter was calculated by linear least squares regression analysis using last three or more non-zero plasma concentration values.
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=86 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=87 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=89 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=88 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z)
ADA-NEGATIVE
|
0.01 h
Standard Deviation 0.007
|
0.01 h
Standard Deviation 0.006
|
0.01 h
Standard Deviation 0.006
|
0.01 h
Standard Deviation 0.006
|
|
PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z)
ADA-POSITIVE
|
0.01 h
Standard Deviation 0.006
|
0.01 h
Standard Deviation 0.003
|
0.01 h
Standard Deviation 0.004
|
0.01 h
Standard Deviation 0.005
|
SECONDARY outcome
Timeframe: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
The terminal half-life will be calculated as 0.693/(lambda-z)
Outcome measures
| Measure |
INTP5 Biosimilar Product
n=86 Participants
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=87 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 1
n=89 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
US Neulasta Dose 2
n=88 Participants
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|---|---|
|
PD Endpoints for Baseline Adjusted ANC: t[1/2]
ADA-NEGATIVE
|
62.25 h
Standard Deviation 28.847
|
64.13 h
Standard Deviation 26.785
|
77.23 h
Standard Deviation 86.239
|
76.02 h
Standard Deviation 59.888
|
|
PD Endpoints for Baseline Adjusted ANC: t[1/2]
ADA-POSITIVE
|
67.03 h
Standard Deviation 41.296
|
69.72 h
Standard Deviation 25.447
|
81.74 h
Standard Deviation 29.981
|
67.02 h
Standard Deviation 22.706
|
Adverse Events
INTP5 Biosimilar Product
US Neulasta Reference Product
Serious adverse events
| Measure |
INTP5 Biosimilar Product
n=100 participants at risk
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=100 participants at risk
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|
|
General disorders
death
|
0.00%
0/100 • 99 Days
|
1.0%
1/100 • Number of events 1 • 99 Days
|
Other adverse events
| Measure |
INTP5 Biosimilar Product
n=100 participants at risk
INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta.
|
US Neulasta Reference Product
n=100 participants at risk
US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product.
|
|---|---|---|
|
Blood and lymphatic system disorders
Eosinophilia
|
1.0%
1/100 • Number of events 1 • 99 Days
|
0.00%
0/100 • 99 Days
|
|
Gastrointestinal disorders
Abdominal pain
|
1.0%
1/100 • Number of events 1 • 99 Days
|
0.00%
0/100 • 99 Days
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/100 • 99 Days
|
2.0%
2/100 • Number of events 2 • 99 Days
|
|
Gastrointestinal disorders
Gastritis
|
1.0%
1/100 • Number of events 1 • 99 Days
|
0.00%
0/100 • 99 Days
|
|
Gastrointestinal disorders
Toothache
|
1.0%
1/100 • Number of events 1 • 99 Days
|
0.00%
0/100 • 99 Days
|
|
Gastrointestinal disorders
Vomiting
|
5.0%
5/100 • Number of events 7 • 99 Days
|
5.0%
5/100 • Number of events 7 • 99 Days
|
|
General disorders
Chills
|
1.0%
1/100 • Number of events 1 • 99 Days
|
0.00%
0/100 • 99 Days
|
|
General disorders
Injection site pain
|
5.0%
5/100 • Number of events 5 • 99 Days
|
4.0%
4/100 • Number of events 4 • 99 Days
|
|
General disorders
Pyrexia
|
2.0%
2/100 • Number of events 2 • 99 Days
|
0.00%
0/100 • 99 Days
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
1.0%
1/100 • Number of events 1 • 99 Days
|
1.0%
1/100 • Number of events 1 • 99 Days
|
|
Injury, poisoning and procedural complications
Face injury
|
1.0%
1/100 • Number of events 1 • 99 Days
|
0.00%
0/100 • 99 Days
|
|
Injury, poisoning and procedural complications
Injury
|
0.00%
0/100 • 99 Days
|
3.0%
3/100 • Number of events 3 • 99 Days
|
|
Investigations
Eosinophil count increased
|
1.0%
1/100 • Number of events 1 • 99 Days
|
0.00%
0/100 • 99 Days
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/100 • 99 Days
|
1.0%
1/100 • Number of events 1 • 99 Days
|
|
Investigations
Human chorionic gonadotropin increased
|
0.00%
0/100 • 99 Days
|
1.0%
1/100 • Number of events 1 • 99 Days
|
|
Investigations
Protein urine present
|
1.0%
1/100 • Number of events 1 • 99 Days
|
1.0%
1/100 • Number of events 1 • 99 Days
|
|
Investigations
Red blood cells urine positive
|
3.0%
3/100 • Number of events 3 • 99 Days
|
0.00%
0/100 • 99 Days
|
|
Investigations
Urine analysis abnormal
|
0.00%
0/100 • 99 Days
|
1.0%
1/100 • Number of events 1 • 99 Days
|
|
Investigations
Urine output decreased
|
1.0%
1/100 • Number of events 1 • 99 Days
|
0.00%
0/100 • 99 Days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
16.0%
16/100 • Number of events 17 • 99 Days
|
15.0%
15/100 • Number of events 16 • 99 Days
|
|
Nervous system disorders
Headache
|
6.0%
6/100 • Number of events 7 • 99 Days
|
13.0%
13/100 • Number of events 13 • 99 Days
|
|
Investigations
Urine abnormality
|
1.0%
1/100 • Number of events 1 • 99 Days
|
0.00%
0/100 • 99 Days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.0%
1/100 • Number of events 1 • 99 Days
|
0.00%
0/100 • 99 Days
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
1.0%
1/100 • Number of events 1 • 99 Days
|
1.0%
1/100 • Number of events 1 • 99 Days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/100 • 99 Days
|
1.0%
1/100 • Number of events 1 • 99 Days
|
|
Skin and subcutaneous tissue disorders
Rash generalized
|
0.00%
0/100 • 99 Days
|
1.0%
1/100 • Number of events 1 • 99 Days
|
|
Skin and subcutaneous tissue disorders
Skin burning sensation
|
0.00%
0/100 • 99 Days
|
1.0%
1/100 • Number of events 1 • 99 Days
|
Additional Information
Dr. Adarsh Kumar Garg, M.B.B.S. Principal Investigator
Lambda Therapeutic Research Ltd.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place