Pharmacokinetic, Immunogenicity, and Safety Evaluation of Pegfilgrastim TPI-120 in Healthy Adults

An Open Label, Randomized, Two-treatment, Two Sequence, Two Period, Crossover, Single Dose, Comparative Pharmacokinetic, Immunogenicity and Safety Study of Pegfilgrastim Comparing TPI-120 Pre-Filled Syringe With Auto- Injector 6 mg/0.6 mL (T) and Fylnetra Pre-filled Syringe 6 mg/0.6 mL (R) Administered Through Subcutaneous Route, in Normal, Healthy, Adult Human Subjects Under Fasting Conditions

The Goal of these study is to assess the comparative pharmacokinetics of Test Product (A): TPI-120 Injection 6 mg/0.6 mL solution in a single dose pre-filled autoinjector, manufactured by Kashiv Biosciences LLC, USA with Reference Product (B): TPI-120 Injection 6 mg/0.6 mL solution in a single dose pre-filled syringe manufactured by Kashiv Biosciences LLC, USA in healthy, adult human subjects and also to assess safety and tolerability of investigational product.

This study is an open label, randomized, two treatment, two sequence, two period, single dose crossover clinical trial designed to compare the pharmacokinetics, immunogenicity, and safety of Pegfilgrastim TPI 120 (Test) administered via pre filled syringe with auto injector and Fylnetra (Reference) administered via pre filled syringe. The study will be conducted in healthy adult human subjects under fasting conditions.

The study aims to enroll a sufficient number of participants to ensure that 180 healthy subjects complete dosing across both periods. Considering the required procedures and a washout period of at least 34 days between the dosing days of Period I and Period II, the total clinical study duration is approximately 51 days from the first check in. Subjects will be randomized into two treatment sequences and will receive a single subcutaneous dose of either the Test or Reference product in each study period.

The primary objective is to assess the pharmacokinetic (PK) comparability of the two Pegfilgrastim formulations by evaluating PK parameters including Cmax, AUCt, AUCi, Tmax, Kel, AUC%Extrap_obs, and tHalf. PK parameters will be calculated using Phoenix® WinNonlin® (Version 8.1.1 or higher) or SAS® (Version 9.4 or higher). Secondary objectives include assessment of safety and tolerability, as well as immunogenicity through anti drug antibody (ADA) evaluations.

Comprehensive safety assessments will be performed throughout the study. A complete physical examination will be conducted at screening and at the end of the study or early termination, while abbreviated physical examinations will occur during admission of each period, on Day 15 of Period I, and prior to discharge in each period. Clinical laboratory evaluations will include hematology, including absolute neutrophil count (ANC), coagulation (PT/INR), clinical chemistry, and urinalysis, performed at defined time points: screening, check in of Period 1, two days prior to Period 2 check in, Day 15 of Period I, and end of study or early termination.

A 12 lead ECG will be performed at screening, on Day 15 of Period I post dose, and at the end of the study or early termination. Safety screening also includes urine drug screens for drugs of abuse (amphetamine/methamphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, methadone, and phencyclidine) and alcohol breathalyzer testing at screening and prior to admission of each study period.

Subjects will be closely monitored for adverse events (AEs), serious adverse events (SAEs), changes in laboratory parameters, vital signs, and any clinically significant abnormalities. Immunogenicity evaluations will be performed at protocol specified time points to assess the presence of ADAs and potential neutralizing antibodies.

This study is designed to generate robust comparative PK, safety, and immunogenicity data to support the evaluation of biosimilar comparability between Pegfilgrastim TPI 120 and Fylnetra under fasting conditions in healthy adult subjects.

Inclusion Criteria:

1. Age: 18 to 55 years of age, both inclusive, at the time of consent.
2. Gender: Male and/or non-pregnant, non-lactating female.
3. Willing to provide written informed consent to participate in the study.
4. Able to communicate effectively with study personnel.
5. Subject having weight greater than or equal to 50 kg
6. BMI: 19.0 to 30.0 kg/m2, both inclusive
7. Non-smoker and non-tobacco/non-nicotine user (i.e., having no past history of smoking and tobacco/nicotine consuming for at least one year prior to screening).
8. Alcohol breathalyzer test result must be negative during screening and prior to Period 1 dosing.
9. Negative urine drug screen including amphetamine/methamphetamine, barbiturates, benzodiazepines, cannabinoid, cocaine, opiates, methadone and phencyclidine during screening and prior to Period 1 dosing.
10. The subject has a normal ECG (12 leads) as per the investigator judgement, at screening and on admission day (before admission) of period 1.
11. Subject complies with injection site evaluation at screening and on admission day (before admission) of period 1.
12. The subject result of hemoglobin is within normal range or ± 5% of medical lab reference range at screening

Exclusion Criteria:

1. History of antibodies or allergic responses to pegfilgrastim, filgrastim or other GCSF stimulant medications or other related drugs, or any of its formulation ingredients.
2. Any infection, cough or fever or suffered an acute illness within 1 week prior to first study drug administration.
3. Subject having hematologic laboratory abnormalities
4. The subject has been hospitalized within three months before the study or during the study
5. The subject has been participating in any clinical study (e.g., pharmacokinetics, bioavailability and bioequivalence studies) within the last 30 days prior to the present study
6. Clinically significant vital sign abnormalities
7. Positive hepatitis screen (includes subtypes B & C) and/or a positive test result for HIV antibody.
8. Study participants who have received a known investigational drug within 30 days or within seven elimination half-lives of the administered drug prior to the initial dose of study drug, whichever is greater.
9. Study participant who has donated blood and/or had a blood loss of approximately 1 unit or 450 mL within 90 days prior to the initial dosing of the study drug and/or study participant who had blood loss, excluding volume drawn at screening for this study, prior to initial dosing of study drug, whichever is greater
10. Study participant who has a condition or is taking or has taken a medication that, in the Investigator's judgment, makes the study participant ineligible or places the study participant at undue risk
11. Any food allergy, intolerance, restriction or special diet that, in the opinion of the principal investigator or sub-investigator, could contraindicate the study participant's participation in this study.
12. Unavailable for any confinement days or scheduled visits.