Pharmacokinetic, Safety, Tolerability, Immunogenicity, and Pharmacodynamic Study of SB12 in Healthy Subjects

Study Overview
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Brief Summary
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This study is to evaluate PK, safety, tolerability, immunogenicity, and PD profiles of SB12, EU sourced Soliris, and US sourced Soliris in healthy subjects.

Official Title
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A Randomised, Double-blind, Three-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics, Safety, Tolerability, Immunogenicity, and Pharmacodynamics of Eculizumab (SB12, EU Sourced Soliris®, and US Sourced Soliris®) in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Eculizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Have a body weight between 70-95 kg and a body mass index between 20.0-29.9 kg/m² Have systolic blood pressure (SBP) ≤ 140 and ≥ 90 mmHg, diastolic blood pressure (DBP) ≤ 95 and ≥ 45 mmHg, and pulse rate ≥ 40 and ≤ 100 beats per minute or assessed as not clinically significant Have physical examination and 12-lead ECG results without clinically significant finding at Screening and Day -1 visits Non-smoker or smoker whose daily smoking does not exceed 10 cigarettes, 3 cigars, or 3 pipes for at least 30 days prior to Screening visit. Subjects should agree to abstain from smoking while resident at the clinical study site. Willing to receive vaccination against N. meningitidis at least 14 days prior to IP administration Male subjects must be willing to abstain from sexual intercourse or willing to use a condom in addition to having their female partner use another form of contraception unless their partner is infertile from the time of IP administration until 5 months after IP administration Must be willing and able to comply with scheduled visits, treatment plan, clinical laboratory tests, and other study procedures including lifestyle considerations Have competence in speaking, writing and comprehending the local language where the study is conducted Exclusion Criteria: Have a history/presence of clinically significant atopic allergy, allergic/hypersensitive reactions, or known or suspected clinically relevant drug hypersensitivity to eculizumab or its excipients Contraindication for IP or non-IP to be used in the study History of N. meningitidis infection Known or suspected hereditary or acquired complement deficiency Clinically significant active infection within 28 days before IP administration Any systemic or local infection, a known risk for developing sepsis and/or known active inflammatory condition Have previously been exposed to eculizumab (Soliris and its biosimilar) Previous treatment with a monoclonal antibody or fusion protein within 9 months prior to IP administration and/or have an evidence of immunogenicity from previous exposure to a monoclonal antibody or fusion protein Have previously been exposed to an immunosuppressive agent or biological agent (any other than a monoclonal antibody or fusion protein) within 120 days prior to IP administration Any of the following abnormal laboratory values at Screening and Day -1 visits: Serum alanine transaminase and/or aspartate transaminase ≥ 1.5 × ULN Serum C-reactive protein ≥ 10 mg/L Serum creatinine > 1.5 × ULN Whole blood cell count < 3000/mm3, absolute lymphocyte count < 800/mm3, and/or absolute neutrophil count ≤ 1500/mm3 Any other laboratory abnormalities assessed as clinically significant by the Investigator Positive test result for hepatitis B surface antigen and/or hepatitis B core antibody, hepatitis C virus antibody, or human immunodeficiency virus at Screening Surgery within 90 days prior to IP administration, and/or operation during study period Average intake of alcoholic beverages of more than 21 units/week for males and 14 units/week for females Drug abuse or a positive urinary drug screening result Have any prescription medicine or over-the-counter medicines (except paracetamol) that might have an effect on the objectives of the study, within 14 days prior to IP administration Donated >100 mL blood or plasma within 28 days prior to IP administration Subject directly involved in the conduct of the clinical study Vulnerable subjects Pregnant or nursing (lactating) women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SB12<br>SB12 (proposed eculizumab biosimilar) | Drug: Eculizumab<br>* Eculizumab Injection. 300 mg, single dose<br>|
| Active Comparator: EU Soliris<br>EU sourced Soliris (eculizumab) | Drug: Eculizumab<br>* Eculizumab Injection. 300 mg, single dose<br>|
| Active Comparator: US Soliris<br>US sourced Soliris (eculizumab) | Drug: Eculizumab<br>* Eculizumab Injection. 300 mg, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCinf | Area under the concentration-time curve from time zero to infinity | Day 1 to Day 64 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUClast | Area under the concentration-time curve from time zero to the last quantifiable concentration | Day 1 to Day 64 | 
| Cmax | Maximum observed serum concentration | Day 1 to Day 64 | 
| Tmax | Time to reach Cmax | Day 1 to Day 64 | 
| Vz | Volume of distribution during terminal phase | Day 1 to Day 64 | 
| λz | Terminal rate constant | Day 1 to Day 64 | 
| T1/2 | Terminal half-life | Day 1 to Day 64 | 
| Clearance | Total body clearance | Day 1 to Day 64 | 
| %AUCextrap | Percentage of AUCinf due to extrapolation from time of last measurable concentration (Tlast) to infinity | Day 1 to Day 64 | 
| Incidence of Treatment-Emergent Adverse Events | Experience at least 1 treatment-emergent adverse event | Day 1 to Day 64 | 
| Incidence of Serious Adverse Events | Experience at least 1 serious adverse event | Day 1 to Day 64 | 
| Incidence of ADA | Incidence of anti-drug antibodies | Day 1 to Day 64 | 
| Incidence NAb | Incidence neutralising antibodies | Day 1 to Day 64 |