Comparison of the Pharmacokinetic and Pharmacodynamic Biosimilarity of CHS-1701 (Coherus Pegfilgrastim) With Neulasta® (Pegfilgrastim)

Study Overview
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Brief Summary
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This is a randomized, double-blind, single-dose, 2-period crossover study in healthy subjects to assess PK, PD, and safety (including immunogenicity) of a single 6 mg subcutaneous (SC) injection of CHS-1701 compared with a single 6 mg SC dose of Neulasta®.

Detailed Description
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This is a randomized, double-blind, single-dose, 2-period crossover study in healthy subjects to assess PK, PD, and safety (including immunogenicity) of a single 6 mg subcutaneous (SC) injection of CHS-1701 compared with a single 6 mg SC dose of Neulasta®. After screening, eligible subjects will be randomly assigned to 1 of 2 treatment sequences; CHS-1701 followed by Neulasta® (Sequence A) or Neulasta® followed by CHS-1701, Sequence B). Treatments will be spaced by a minimum of 6 weeks apart (but no more than 8 weeks). Subjects will be admitted to the Clinical Pharmacology Unit (CPU) on Day -1 (Period 1) and will be confined through Hour 96 postdose (a total of approximately 4.5 days and 5 nights). Blood samples will be collected at specified time points postdose for plasma PK and PD measurements and the subjects will be closely monitored for safety. Following discharge on the morning of Day 5 (Period 1) subjects will return to the clinic for additional PK, PD and safety follow up--daily through Day 9 and at stated interval time points thereafter. The single dose of the alternate blinded study drug will be given after 6 (but no more than 8) weeks of observation and washout and the above procedures will be repeated (Period 2). A Follow up Visit will take place 41 (±1) days after the second dose.

Official Title
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A Randomized, Double-Blind, Crossover Study to Compare the Pharmacokinetic and Pharmacodynamic Biosimilarity of CHS-1701 (Coherus Pegfilgrastim) With Neulasta® in Healthy Subjects

Conditions
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Bioequivalence

Intervention / Treatment
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* Drug: CHS-1701
* Drug: Pegfilgrastim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or female of ages 18 to 50 inclusive Body weight > 50 kg (110 lb.) and body mass index between 18 and 32 kg/m2 inclusive Medically healthy with clinically insignificant findings based on medical history, 12-lead ECG, and physical examination Negative urine pregnancy test in women of childbearing potential Exclusion Criteria: Previous exposure to pegfilgrastim or filgrastim, or known allergy to PEG (polyethylene glycol) Chemistry and hematology values outside protocol specified range Current or previous cancer, diabetes, or any clinically significant cardiovascular, metabolic, renal, hepatic, gastrointestinal, hematologic, respiratory, dermatological, neurological, psychiatric, or other disorder History of chronic or acute respiratory illness within the past 4 weeks Positive urine drug or alcohol screen or unwillingness to abstain from alcohol or recreational drugs for the duration of study participation No prescription or nonprescription drugs during the study Participation in an investigational clinical study within 30 days prior to screening Known or suspected allergic reaction to latex

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHS-1701/Neulasta<br>CHS-1701 followed by Neulasta (crossover) | Drug: CHS-1701<br> <br> Drug: Pegfilgrastim<br> <br> * Other names: Neulasta;|
| Experimental: Neulasta/CHS-1701<br>Neulasta followed by CHS-1701 (crossover) | Drug: CHS-1701<br> <br> Drug: Pegfilgrastim<br> <br> * Other names: Neulasta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biosimilarity as measured by absolute neutrophil count (ANC) | The primary objective of this study is to assess the biosimilarity of CHS-1701 with Neulasta® based on the pharmacokinetics (PK) of pegfilgrastim and the pharmacodynamic (PD) response as measured by absolute neutrophil count (ANC). | 84 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Profile: Cmax (tmax), AUC0-t, and t1/2 | Characterization of the PK profile of CHS-1701 using standard parameters (Cmax (tmax), AUC0-t, and t1/2) | 84 Days | 
| Safety Profile as assessed by clinical adverse events (AEs), laboratory variables, vital signs, incidence of antidrug antibodies (ADAs), and local injection site reactions (ISRs). | Characterization of the safety profile and tolerance of CHS-1701, as assessed by clinical adverse events (AEs), laboratory variables, vital signs, incidence of antidrug antibodies (ADAs), and local injection site reactions (ISRs). | 84 Days |