Immunogenicity and Pharmacodynamic of B12019 and Neulasta® in Healthy Subjects

Multiple-doses, Randomised, Double-blind, Three-periods, Two-sequences Crossover Study to Assess the Immunogenicity and Pharmacodynamic Comparability of a Biosimilar Pegfilgrastim (B12019) and the Reference Product Neulasta® in Healthy Subjects

Multiple-doses, randomised, double-blind, three-periods, two-sequences crossover study to assess the immunogenicity and pharmacodynamic comparability of a biosimilar pegfilgrastim (B12019) and the reference product Neulasta® in healthy subjects

Inclusion Criteria:

1. Healthy male subjects, between 18 and 55 years of age (inclusive).
2. BMI between 20.0 and 30.0 kg/m² (inclusive).
3. Weight between 60 and 100 kg (inclusive).
4. Non-smoker for at least 3 months or mild smokers with a consumption of less than 5 cigarettes (or equivalent) per day prior to study start.
5. Healthy subjects as determined by medical history, physical examination including vital signs, ECG and clinical laboratory testing.
6. Able to comply with protocol requirements, including overnight stays, blood sample collections as defined in the protocol and to participate in the entire trial period.
7. Subjects who are able and willing to give written informed consent.
8. Male subject and his female spouse/partner who is of childbearing potential must be using effective contraception starting at screening and continue throughout the clinical study period.
9. Male subject must not donate sperm starting at screening and throughout the clinical study period and for 3 months after final study drug administration.

Exclusion Criteria:

History of:

1. Evidence in the subject's medical history or in the medical examination of any clinically significant hepatic, renal, gastrointestinal, cardiovascular, pulmonary, haematological, central nervous system diseases or other significant acute or chronic diseases, especially hereditary fructose intolerance, which might influence either the safety of the subject or the absorption, metabolism or excretion of the active agent under investigation.
2. Subjects with clinically relevant neurologic or psychiatric illness.
3. Subjects with clinically relevant allergy (except for untreated, asymptomatic, seasonal allergies at time of dosing).
4. Previous exposure to pegfilgrastim.
5. Known hypersensitivity to Escherichia coli-derived proteins, pegfilgrastim, filgrastim or any other component of B12019 or Neulasta® as listed in section 7.2.
6. History of allergy to any recombinant protein.
7. History of cancer.
8. History of haematological disease, including sickle cell disorder.
9. History of pulmonary infiltrates or pneumonia within 6 months before the first study drug administration.
10. Known anti-drug antibodies to filgrastim or pegfilgrastim, including known antibodies to PEG as a consequence of exposure to PEG other than pegfilgrastim (e.g. cosmetics, etc.).
11. Subjects not willing or able to comply with the food and beverage restrictions (grapefruit/pomelo, starfruit, poppy seeds).