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.
- Conditions
- ImmunogenicityHealthy Volunteers
- Interventions
- Combination Product: INTP5Combination Product: US Neulasta
- Registration Number
- NCT04015232
- Lead Sponsor
- Intas Pharmaceuticals, Ltd.
- Brief Summary
The study was an assessor-blind, balanced, parallel, randomized, two-treatment, comparative immunogenicity study of multiple doses of subcutaneous (SC) Pegfilgrastim injection (6 mg/0.6 mL; Intas Pharmaceuticals Ltd. proposed biosimilar INTP5 compared to innovator product, US-Neulasta) in healthy, adult, human subjects under fed conditions.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 200
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description INTP5 biosimilar product INTP5 INTP5 subcutaneously at a dose of 6 mg/0.6 mL. US Neulasta reference product US Neulasta US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
- Primary Outcome Measures
Name Time Method Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies. Samples (8 mL each) were withdrawn at screening, at pre-dose and at 336 (D-15, Week 2), 504 (D-22, Week 3, within 60 minutes before 2nd dose), 840 (D-36, Week 5), 1176 (D-50, Week 7), 1680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.
- Secondary Outcome Measures
Name Time Method PK Endpoints: Pegfilgrastim T[Max] 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. The time of observing the peak concentration, calculated from the serum concentration vs. time profile of the individual subjects.
PK Endpoints: Pegfilgrastim λz (Lambda-z) 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. 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.
PD Endpoints for Baseline Adjusted ANC: t[1/2] 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. The terminal half-life will be calculated as 0.693/(lambda-z)
PK Endpoints: Pegfilgrastim R^2 Adjusted 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. 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.
PK Endpoints: Pegfilgrastim t[1/2] 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. The terminal half-life calculated using the formula 0.693/(lambda-z)
PD Endpoints for Baseline Non-adjusted ANC: T[Max] 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. Area under the ANC versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.
PD Endpoints for Baseline Adjusted ANC: E[Max] 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. Maximum measured absolute neutrophil count (ANC).
PK Endpoints: Pegfilgrastim AUC[0-t] 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. 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.
PD Endpoints for Baseline Non-adjusted ANC: E[Max] 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. Maximum measured absolute neutrophil count (ANC).
PK Endpoints: Pegfilgrastim C[Max] 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. 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.PK Endpoints: Pegfilgrastim AUC[0-∞] 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. 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.
PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t] 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. Time to reach the maximum measured absolute neutrophil count (ANC)
PD Endpoints for Baseline Adjusted ANC: AUEC[0-t] 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. Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.
PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z) 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. 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.
PK Endpoints: Pegfilgrastim AUC[_%Extrap_Obs] 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. The residual area in percentage determined by the formula, \[(AUC\[0-infinity\]-AUC\[0-t\])/AUC\[0-infinity\]\] x 100.
PD Endpoints for Baseline Adjusted ANC: T[Max] 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. Time to reach the maximum measured absolute neutrophil count (ANC)
Trial Locations
- Locations (1)
Lambda Therapeutic Research Ltd.
🇮🇳Ahmedabad, Gota, India