A Comparative Study to Evaluate the Effect of HSP-130, US-approved Neulasta and EU-approved Neulasta in Healthy Participants

Study Overview
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Brief Summary
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This study is for healthy participants. This study tests single dose of the research drug HSP-130 against two existing approved drugs United States - approved Neulasta and European Union-approved Neulasta.

Detailed Description
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There will be 25 healthy participants in each of the six sequence groups. A total of 150 participants will be studied in one site in Australia. In addition to the 150 participants included, alternate subjects will be asked to come to the site on the day prior to when dosing is scheduled to begin. There will be 3 treatment options with 3 study dosing periods (1, 2 and 3) and at least 56 days between each treatment. The subject once asked to take part in the study will be assigned by chance (randomized) to one of the sequence groups as mentioned above (1, 2, 3, 4, 5, or 6).

Official Title
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A Phase 1 Study Assessing The Pharmacodynamic And Pharmacokinetic Equivalence Of HSP-130 With US-approved Neulasta (Registered) And EU-approved Neulasta (Registered) Administered As A Single Subcutaneous Dose To Healthy Volunteers

Conditions
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Neutropenia

Intervention / Treatment
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* Drug: HSP-130
* Drug: US-approved Neulasta
* Drug: EU-approved Neulasta


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provides written informed consent approved by an Independent Ethics Committee (IEC) prior to any study related activities Healthy male or female volunteers between 18 and 65 years of age (both inclusive) Body mass index (BMI) between 19 and 30 kg/m^2, inclusive, and body weight of not <50 kg or >100 kg Non-smoker (defined as a subject who has not smoked and has not used nicotine containing products for at least 3 months prior to study drug administration and has a negative urine screen for cotinine) at Screening Female subjects of childbearing potential and male subjects and their partners of childbearing potential, agree to pregnancy prevention throughout the duration of the study (through the Follow-up Visit). Subjects and their partners must agree to use of an effective method of contraception, to avoid impregnation of females throughout the course of the study. Subjects using oral contraceptives must be on a stable regimen for at least 3 months prior to Screening. Adequate forms of contraception to be used include hormonal contraceptives (oral, patch, depot), intrauterine devices (IUD), barrier contraceptive methods, such as diaphragm, cervical cap/shield, male condoms and female condoms.Sexually active subjects must use contraception while on study drug from admission to the Follow-up Visit. Male subjects must also refrain from donating sperm from admission to the Follow-up visit 6. Willing and able to comply with the requirements of the protocol and available for the planned duration of the study Exclusion Criteria: Any active systemic or immunologic disease or condition, including but not limited to the following general categories: cardiovascular/pulmonary, hepatorenal, or systemic infection, or lactation History of, or current, malignancy with the exception of adequately treated squamous or basal cell carcinoma of the skin or cervical carcinoma in situ within 5 years Any disease or condition that might interfere with the absorption, distribution, metabolism, or excretion of the study drug or would place the subject at increased risk Hematologic laboratory abnormalities including leukocytosis (defined as total leukocytes >11,000/μL), leukopenia (defined as total leukocytes <4000/μL), neutropenia (defined as ANC <1500/μL) or thrombocytopenia (defined as platelet count of <150/μL) Clinically significant, as judged by the investigator, vital sign or 12-lead ECG abnormality History of biological growth factor exposure, including but not limited to filgrastim and other granulocyte-colony stimulating factors in the context of treatment, prophylaxis, peripheral blood stem cell mobilization, or previous investigational study setting. This also includes exclusion for history of interferon, epoetin, and intravenous immunoglobulin (IVIG) exposure Receipt of live vaccination, or exposure to communicable viral diseases such as, varicella, mumps, or measles within the 4 weeks prior to Screening Surgery within the 4 months prior to Screening Use of any prescription medicine (with the exception of contraceptives) within 7 days or at least 5 half-lives, whichever is longer. Use of oral or parenteral anticoagulant or antiplatelet agents and corticosteroids should be specifically queried Administration of a drug by depot injection (with exception of depot contraception) within 30 days prior to Randomization or 5 half-lives of that drug, whichever is longer Use of over the counter medications, including aspirin and non-steroidal anti-inflammatory drugs, or natural preparations (dietary supplement or herbal product) within 7 days or at least 5 half-lives, whichever is longer. Vitamins and calcium are allowed (not to exceed 100% Daily Value) History of drug or alcohol abuse within 2 years prior to Randomization, as determined by the investigator or a positive urine screen for drugs of abuse (UDS) at Screening. Screening for drugs of abuse will minimally include cannabinoids, opiates, barbiturates, amphetamines, cocaine, benzodiazepines, and alcohol Drug sensitivity, allergic reaction to, or known hypersensitivity/idiosyncratic reaction to Escherichia coli-derived proteins, filgrastim, other granulocyte-colony stimulating factors, or pegylated agents History of splenic rupture (or subject who is asplenic), pulmonary infiltrate or pneumonia, sickle cell disease, chronic neutropenia, thrombocytopenia, or vasculitis Any clinically significant, as determined by the investigator, abnormal laboratory evaluations, including human immunodeficiency virus antibody (HIVAb), hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), and liver function including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 1.5 the upper limit of normal taken at Screening. Negative HIVAb status will be confirmed at Screening and the results will be maintained confidentially by the study site Donated or lost 475 mL or more blood volume (including plasmapheresis) or had a transfusion of any blood product within 3 months prior to Screening Participated in another clinical research study with administration of investigational drug within 30 days prior to Randomization Potentially not be able to comply with the requirements of this clinical trial, to communicate effectively with study personnel, or is considered by the Investigator, for any reason, to be an unsuitable candidate for the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment A<br>HSP-130, 6 mg, single subcutaneous (SC) injection in the deltoid region | Drug: HSP-130<br> <br> * Other names: Pegylated filgrastim;|
| Other: Treatment B<br>US-approved Neulasta, 6 mg, single SC injection in the deltoid region | Drug: US-approved Neulasta<br> <br> * Other names: Pegfilgrastim, Amgen;|
| Other: Treatment C<br>EU-approved Neulasta, 6 mg, single SC injection in the deltoid region | Drug: EU-approved Neulasta<br> <br> * Other names: Pegfilgrastim, Amgen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the effect versus time curve for absolute neutrophil count (ANC) from the time of dose administration to 288 hours after dose administration (AUECANC) |  | Within 1 hour prior to dose administration and at 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, and 288 hours post-dose. | 
| Maximum observed value for ANC (ANC_Cmax) |  | Within 1 hour prior to dose administration and at 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, and 288 hours post-dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of maximum value for ANC (ANC_Tmax) |  | Within 1 hour prior to dose administration and at 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, and 288 hours post-dose. | 
| Area under the serum pegylated filgrastim versus time curve from the time of dose administration to time infinity (AUC0-∞) |  | Within 1 hour prior to dose and at 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, and 288 hours post-dose. | 
| Maximum observed serum pegylated filgrastim concentration (Cmax) |  | Within 1 hour prior to dose and at 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, and 288 hours post-dose. | 
| Area under the serum pegylated filgrastim versus time curve from the time of dose administration to the time of last measurable concentration (AUC0-t) |  | Within 1 hour prior to dose and at 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, and 288 hours post-dose. | 
| Time to maximum serum pegylated filgrastim concentration (Tmax) |  | Within 1 hour prior to dose and at 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, and 288 hours post-dose. | 
| Elimination half-life (t1/2) |  | Within 1 hour prior to dose and at 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, and 288 hours post-dose. | 
| Elimination rate constant (λz) |  | Within 1 hour prior to dose and at 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, and 288 hours post-dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HSP-130, Pharmacodynamic and Pharmacokinetic equivalence, Pegfilgrastim