Comparative, Pharmacokinetic and Pharmacodynamic Study of... | NCT04014062

Status Module

Name	Class
Lambda Therapeutic Research Ltd.	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
INTP5 Period I Crossover	Experimental	Period I: Subjects received a single dose of INTP5 subcutaneously at a dose of 6 mg/0.6 mL. Period II: After the first treatment cycle and a six week wash out period, patients received a single dose of US Neulasta.	Combination Product: INTP5 Combination Product: US Neulasta
US Neulasta Period I Crossover	Active Comparator	Period I: Subjects received a single dose US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. Period II: After the first treatment cycle and a six week wash out period, patients received a single dose of INTP5.	Combination Product: INTP5 Combination Product: US Neulasta

Name	Type	Description	Arm Group Labels	Other Names
INTP5	Combination Product	INTP5: A proposed pegfilgrastim biosimilar to US Neulasta.	INTP5 Period I Crossover US Neulasta Period I Crossover

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Pharmacokinetic (PK) Endpoints: Pegfilgrastim C[Max]	Maximum measured serum concentration, calculated from the serum concentration vs. time profile of the individual subjects.	Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.
Pharmacokinetic (PK) Endpoints: Pegfilgrastim AUC[0-infinity]	Area under the serum concentration versus time curve from time zero to infinity. Where AUC[0-infinity]= AUC[0-t] + Ct/λz(lambda-z), Ct is the last measurable concentration and λz(lambda-z) is the terminal rate constant.	Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.
Pharmacodynamic (PD) Endpoints: E[Max] for Baseline Non-adjusted ANC	Maximum measured absolute neutrophil count (ANC).	Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13), 312 (D-14), 336 (D-15), 360 (D-16) and 504 (D-22) hours post-dose.
Pharmacodynamic (PD) Endpoints: AUEC[0-t] for Baseline Non-adjusted ANC	Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.	Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13), 312 (D-14), 336 (D-15), 360 (D-16) and 504 (D-22) hours post-dose.

Secondary Outcomes

Measure	Description	Time Frame
PK Endpoint: Pegfilgrastim AUC[0-t]	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.	Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.

Other Outcomes

Measure	Description	Time Frame
Immunogenicity: Presence of Anti-drug Antibodies	Evaluation of immunogenicity is carried out in a tiered fashion: Screening assay to assess if samples were positive or negative for anti-PegG-CSF. 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. Titer assay was performed to determine titer of the anti-PEG-GCSF antibody samples. 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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Normal, healthy adult human volunteers between 18 and 45 years of age (both inclusive) living in and around Ahmedabad city or western part of India.
Having body weight ≥50 kg and body mass index (BMI) between 18.5 and 29.9 (both inclusive), calculated as weight in kg/height in meter^2.
Not having any significant disease in medical history or clinically significant abnormal findings during screening, abdominal ultrasonography, medical history, clinical examination, laboratory evaluations, 12-lead ECG and chest X-ray (posterior-anterior view; within the last 6 months) recordings.
Volunteer who is a Non-smoker
Able to understand and comply with the study procedures, in the opinion of the investigator.
Able to give voluntary written informed consent for participation in the trial.
In case of female subjects:
- Surgically sterilized at least 6 months prior to study participation;- Or - If a woman of childbearing potential is willing to use a suitable and effective double barrier contraceptive method or intra uterine device during the study.
- Serum pregnancy test (for female subjects) must be negative.

Exclusion Criteria:

Known hypersensitivity to the study drug or its constituents and/or hypersensitivity to E. coli derived proteins, and/or previous exposure to the study drug.
History or presence of any disease or condition which might compromise the haemopoietic, renal, hepatic, endocrine, pulmonary, central nervous, cardiovascular, immunological, dermatological, gastrointestinal or any other body system.
Known case of hereditary fructose intolerance.
Subjects with latex allergies will be excluded as the needle cover on the single-use pre-filled syringe contains dry natural rubber (latex).
Any clinically significant laboratory finding including ANC, platelet, RBC count or hemoglobin level at the time of screening.
Prior exposure to any peptide colony stimulating or growth factor, including erythropoietin, filgrastim or Pegfilgrastim; Prior exposure to vaccines, immunoglobulin preparations, or immunomodulator's within the past 6 months prior to receiving the first dose; evidence of E. coli diarrhea or diseases within 3 months.
Any history or presence of asthma (including aspirin-induced asthma) or nasal polyp or NSAIDs induced urticaria.
Subjects with a history of pulmonary infiltrate or pneumonia in the last 6 months.
History of any hematologic disease including sickle cell disorders.
Smokers, or who have smoked within last six months prior to start of the study.
Ingestion or use of any prescribed medication at any time within 1 month prior to receiving first dose in Period-I.
Receipt of over-the-counter medicines which have not yet cleared from the body (5 half-lives must have passed for the medicine to be considered to have cleared from the body).
A recent history of harmful use of alcohol, i.e. alcohol consumption of more than 14 standard drinks per week for men and more than 7 standard drinks per week for women (A standard drink is defined as 360 mL of beer or 150 mL of wine or 45 mL of 40% distilled spirits, such as rum, whisky, brandy etc.) or consumption of alcohol or alcoholic products within 72 hours prior to receiving study medicine in Period-I.
Use of any recreational drugs or history of drug addiction or testing positive in pre-study drug scans.
Donation of blood (1 unit or 350 mL) or equivalent amount of blood substitute. Receipt of an investigational medicinal product or participation in a drug research study within a period of 180 days prior to the first dose of study medication. Elimination half-life of the study drug should be taken into consideration for inclusion of the subject in the study.
Positive result for human immunodeficiency virus (HIV I &/or II) and/or hepatitis B and C tests.
History or presence of cancer because of which anticipated life span is less than 5 years as per the investigator's assessment.
History or presence of psychiatric disorders.
Presence of tattoo or scars or any type of skin lesions due to infection, burning, wound or inflammation at the proposed site of injection.
An unusual diet, for whatever reason (e.g. low-sodium), for 4 weeks prior to receiving the study medicine in Period-I. In any such case, subject selection will be at the discretion of the Principal Investigator.
Consumption of grape fruit or grape fruit products within 72 hours prior to receiving study drug in Period-I.
A history of difficulty in donating blood.
Females, pregnant or lactating, or planning to become pregnant during the course of the study or found positive in pregnancy test at screening.
Any infections in the last 4 weeks before receiving study medication in Period-I.

Name	Affiliation	Role
Anshul Attrey, M.D.	Lambda Therapeutic Research Ltd.	Principal Investigator
Vinu Jose, M.D.	Intas Pharmaceuticals, Ltd.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Lambda Therapeutic Research Ltd.		Ahmedabad	Gota	Ahmedabad-382481	India

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	INTP5 Period I, US Neulasta Period II Crossover	Period I: Subjects received a single dose of INTP5 subcutaneously at a dose of 6 mg/0.6 mL. Period II: After the first treatment cycle and a six week wash out period, patients received a single dose of US Neulasta. INTP5: INTP5: A proposed pegfilgrastim biosimilar to US Neulasta. US Neulasta: US Neulasta: FDA-approved pegfilgrastim innovator product.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 2, 2017	Jul 19, 2019

Arm/Group Information

ID	Title	Description
BG000	INTP5 Period I, US Neulasta Period II Crossover	Period I: Subjects received a single dose of INTP5 subcutaneously at a dose of 6 mg/0.6 mL. Period II: After the first treatment cycle and a six week wash out period, patients received a single dose of US Neulasta. INTP5: INTP5: A proposed pegfilgrastim biosimilar to US Neulasta. US Neulasta: US Neulasta: FDA-approved pegfilgrastim innovator product.
BG001	US Neulasta Period I, INTP5 Period II Crossover	Period I: Subjects received a single dose US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. Period II: After the first treatment cycle and a six week wash out period, patients received a single dose of INTP5. INTP5: INTP5: A proposed pegfilgrastim biosimilar to US Neulasta. US Neulasta: US Neulasta: FDA-approved pegfilgrastim innovator product.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00071 BG00171 BG002142

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Pharmacokinetic (PK) Endpoints: Pegfilgrastim C[Max]

Maximum measured serum concentration, calculated from the serum concentration vs. time profile of the individual subjects.

Posted

Mean

Standard Deviation

ng/mL

Samples withdrawn at 1 hour pre-dose , at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 (D-2), 26, 30, 36, 42, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 240 (D-11), 288 (D-13), 336 (D-15) & 504 (D-22) hours post-dose.

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Units	Counts
Participants	OG000129 OG001129

Title

Denominators

Categories

Title	Measurements
	OG000474.269± 240.2247 OG001425.578± 219.8054

Primary

Pharmacokinetic (PK) Endpoints: Pegfilgrastim AUC[0-infinity]

Area under the serum concentration versus time curve from time zero to infinity. Where AUC[0-infinity]= AUC[0-t] + Ct/λz(lambda-z), Ct is the last measurable concentration and λz(lambda-z) is the terminal rate constant.

3 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PK parameters

Posted

Mean

Standard Deviation

ng.h/mL

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimilar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Primary

Pharmacodynamic (PD) Endpoints: E[Max] for Baseline Non-adjusted ANC

Maximum measured absolute neutrophil count (ANC).

Posted

Mean

Standard Deviation

x10^3 cells/uL

Samples were withdrawn 1 hour pre-dose and at 6, 12, 24 (D-2), 36, 48 (D-3), 60, 72 (D-4), 96 (D-5), 120 (D-6), 144 (D-7), 168 (D-8), 192 (D-9), 216 (D-10), 240 (D-11), 288 (D-13), 312 (D-14), 336 (D-15), 360 (D-16) and 504 (D-22) hours post-dose.

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Units	Counts
Participants	OG000

Primary

Pharmacodynamic (PD) Endpoints: AUEC[0-t] for Baseline Non-adjusted ANC

Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.

5 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PD parameters.

Posted

Mean

Standard Deviation

x10^3 cells*h/uL

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Units	Counts

Secondary

PK Endpoint: Pegfilgrastim AUC[0-t]

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.

3 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PK parameters

Posted

Mean

Standard Deviation

ng.h/mL

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Units	Counts

Secondary

PK Endpoint: Pegfilgrastim T[Max]

The time of observing the peak concentration, calculated from the serum concentration vs. time profile of the individual subjects.

Posted

Mean

Standard Deviation

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Units	Counts
Participants	OG000

Secondary

PK Endpoint: Pegfilgrastim λz(Lambda-z)

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.

3 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PK parameters

Posted

Mean

Standard Deviation

1/h

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Secondary

PK Endpoint: Pegfilgrastim R^2 Adjusted

Goodness of fit statistic for the terminal phase, adjusted for the number of points used in the estimation of λz.

R^2 is the coefficient of Determination and can range from 0 to 1,; with higher values indicating greater predictability.

3 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PK parameters

Posted

Mean

Standard Deviation

Coefficient of Determination

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Secondary

PK Endpoint: Pegfilgrastim t[1/2]

The terminal half-life calculated using the formula 0.693/λz(lambda-z).

Posted

Mean

Standard Deviation

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Units	Counts
Participants	OG000

Secondary

PK Endpoint: Pegfilgrastim AUC[_Percent_Extrap_Obs]

The residual area in percentage determined by the formula, [(AUC[0-infinity]-AUC]0-t])/AUC0-infinity] x 100.

3 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PK parameters

Posted

Mean

Standard Deviation

percent of AUC

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Units	Counts
Participants

Secondary

PD Endpoint: T[Max] for Baseline Non-adjusted ANC

Time to reach the maximum measured absolute neutrophil count (ANC)

Posted

Mean

Standard Deviation

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Units	Counts
Participants	OG000

Secondary

PD Endpoint: E[Max], Baseline-adjusted ANC

Maximum measured absolute neutrophil count (ANC)

Posted

Mean

Standard Deviation

x10^3 cells/uL

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Units	Counts
Participants	OG000

Secondary

PD Endpoint: AUEC[0-t], Baseline-adjusted ANC

Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.

5 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PD parameters.

Posted

Mean

Standard Deviation

x10^3cells*h/uL

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Units	Counts

Secondary

PD Endpoint: T[Max], Baseline-adjusted ANC

Time to reach the maximum measured absolute neutrophil count (ANC)

Posted

Mean

Standard Deviation

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Units	Counts
Participants	OG000

Secondary

PD Endpoint: λz(Lamda-z) and Baseline-adjusted ANC

First order rate constant associated with the terminal (log-linear) portion of the curve. This is estimated via linear regression of time vs. log concentration.

This parameter will be calculated by linear least squares regression analysis using at least last three or more non-zero values.

5 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PD parameters.

Posted

Mean

Standard Deviation

1/h

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Secondary

PD Endpoint: t[1/2] for Baseline-adjusted ANC

The terminal half-life will be calculated as 0.693/λz(lamda-z).

5 subjects having three consecutive missing samples in the elimination phase were excluded from the statistical analysis of AUC0-t and other elimination phase dependent PD parameters.

Posted

Mean

Standard Deviation

ID	Title	Description
OG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II.
OG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II.

Units	Counts
Participants

Other Pre-specified

Immunogenicity: Presence of Anti-drug Antibodies

Evaluation of immunogenicity is carried out in a tiered fashion:

Screening assay to assess if samples were positive or negative for anti-PegG-CSF.
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.
Titer assay was performed to determine titer of the anti-PEG-GCSF antibody samples.
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.

Only a fraction of the population was tested for Immunogenicity. Only participants that displayed treatment related AEs with plausible immune-mediated pathology were analysed for immunogenicity. The data below represents the outcomes for the fraction of each arm that was tested.

Posted

Count of Participants

Participants

0-71 Days

ID	Title	Description
OG000	INTP5 Treatment	Period I: Subjects received a single dose of INTP5 subcutaneously at a dose of 6 mg/0.6 mL. Period II: After the first treatment cycle of US Neulasta and a six week wash out period, patients received a single dose of INTP5 INTP5: A proposed pegfilgrastim biosimilar to US Neulasta. US Neulasta: FDA-approved pegfilgrastim innovator product.
OG001	US Neulasta Treatment	Period I: Subjects received a single dose US Neulasta subcutaneously at a dose of 6 mg/0.6 mL. Period II: After the first treatment cycle of INTP5 and a six week wash out period, patients received a single dose of US Neulasta. INTP5: A proposed pegfilgrastim biosimilar to US Neulasta. US Neulasta: FDA-approved pegfilgrastim innovator product.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	INTP5 Treatment	INTP5: A proposed pegfilgrastim biosimiar to US Neulasta. Outcomes Measures were grouped by treatment. This Group includes patients that received INTP5 in either Period I or Period II. Given that this was a crossover design, AE totals for the entire study are reported comprehensively for Period I (71 Subjects) and Period II (65 Subjects) combined for the 136 subjects who received this treatment. Due to participant dropout between treatments, the number at risk for a given treatment is lower than the starting population for the study.	0	136	0	136	39	136
EG001	US Neulasta Treatment	US Neulasta: FDA approved pegfilgrastim innovator product. Outcomes Measures were grouped by treatment. This Group includes patients that received US Neulasta in either Period I or Period II. Given that this was a crossover design, AE totals for the entire study are reported comprehensively for Period I (71 Subjects) and Period II (64 Subjects) combined for the 135 subjects who received this treatment. Due to participant dropout between treatments, the number at risk for a given treatment is lower than the starting population for the study.	0	135	0	135	39	135

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Lacrimation increased	Eye disorders	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk
Hyperchlorhydria	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected136 at risk EG0011 events1 affected135 at risk
Toothache	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0004 events4 affected136 at risk EG0012 events2 affected135 at risk
Injection site pain	General disorders	Systematic Assessment	EG0002 events2 affected136 at risk EG0015 events5 affected135 at risk
Pyrexia	General disorders	Systematic Assessment	EG0001 events1 affected136 at risk EG0013 events3 affected135 at risk
Injury	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk
Blood creatinine increased	Investigations	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk
Haemoglobin decreased	Investigations	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk
Human chorionic gonadotropin increased	Investigations	Systematic Assessment	EG0002 events2 affected136 at risk EG0013 events3 affected135 at risk
Platelet count decreased	Investigations	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk
Protein urine present	Investigations	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk
Red blood cells urine	Investigations	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk
Red blood cells urine positive	Investigations	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00017 events16 affected136 at risk EG00119 events19 affected135 at risk
Headache	Nervous system disorders	Systematic Assessment	EG00012 events12 affected136 at risk EG00112 events12 affected135 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 events2 affected136 at risk EG0011 events1 affected135 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk