Comparison of Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Bmab 1000 and Prolia® in Normal Healthy Volunteers: DENARIUS: DENosumab Pharmacokinetic equivAlence tRIal in Healthy volUnteerS

Study Overview
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Brief Summary
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This study is to compare the Pharmacokinetics, Pharmacodynamics, safety, and tolerability of Bmab 1000 and Prolia® in normal healthy volunteers.

Detailed Description
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This study will consist of 2 study periods: Screening period (4 weeks) and Treatment period (Dosing and follow-up). In this double-blind, 2-arm study, the eligible subjects will be randomized in a 1:1 ratio to receive either Bmab 1000 or Prolia® on Day 1. The interventions (Bmab 1000 or Prolia®) will be administered subcutaneously. End-of-study visit will be at Week 36 post randomization. The total duration of study participation for a subject will be up to 40 weeks.

Official Title
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A Randomized, Double-blind, Two-arm, Single-dose, Parallel-Group Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Bmab 1000 and Prolia® in Normal Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: Bmab 1000
* Biological: Prolia®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gender: Male or Female Age: Male subjects: 28-55 years, inclusive at screening; Female subjects: 28-45 years, inclusive at screening. Weight: For non-Japanese subjects 60.0-95.0 kg, inclusive at screening. For Japanese subjects 55.0-95.0 kg, inclusive at screening. Body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive, at screening. Vital signs showing no clinically relevant deviations according to the Investigator's judgment or their designee's. In the case of subjects > 45 year-old, if a value of SBP above 145 mmHg is confirmed on rechecking the BP after a period of rest, this subject will not be included in the study. 12-lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the Investigator or their designee. Exclusion Criteria: Evidence of clinically relevant pathology: Like have a history of and/or current clinically significant gastrointestinal, renal, hepatic, cardiovascular, haematological, pulmonary, neurologic, metabolic, psychiatric disorder, drug or alcohol abuse, or allergic disease excluding mild asymptomatic seasonal allergies. Have a history of malignancy (including lymphoma, leukaemia, and skin cancer). Unable to follow protocol instructions or not likely to complete the study in the opinion of the Investigator or their designee. History of relevant drug and/or food allergies (including hypersensitivity to any recombinant protein drug or any of the constituents of denosumab, or latex allergy or hereditary problems of fructose intolerance). Known history of previous exposure to denosumab. Have previously been exposed to a monoclonal antibody or fusion protein (other than denosumab) within 270 days (or 5 half-lives whichever is the longest) prior to randomization and/or there is confirmed evidence or clinical suspicion of immunogenicity from previous exposure to a monoclonal antibody or fusion protein. Prior diagnosis of bone disease, or any condition that will affect bone metabolism such as, but not limited to: osteoporosis, osteogenesis imperfect, hyperparathyroidism, hyperthyroidism, hypothyroidism, osteomalacia, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, current flare-up of osteoarthritis and/or gout, active malignancy, renal disease (defined as glomerular filtration rate < 60 mL/min), Paget's disease of the bone, recent bone fracture (within 6 months), malabsorption syndrome. Any use of the following bone modifying medications, with no limitation on time since administration: e.g.intravenous bisphosphonates, strontium, fluoride (if administered in treatment of osteoporosis),romosozumab, teriparatide or any parathyroid hormone analogs, calcitonin, and cinacalcet.

Ages Eligible for Study
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Minimum Age: 28 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bmab 1000, A single 60 mg dose of Bmab 1000 administered by subcutaneous injection.<br> | Biological: Bmab 1000<br>* 60mg/ml Prefilled syringe single dose<br>|
| Active Comparator: Prolia®, A single 60 mg dose of Prolia® administered by subcutaneous injection.<br> | Biological: Prolia®<br>* 60mg/ml Prefilled syringe 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 infinity) | Area under the concentration-time curve from time zero to infinity | 0 to 36 week | 
| AUClast (Area Under the Concentration last) | Area under the concentration-time curve from time zero to last quantifiable concentration | 0 to 36 week | 
| Cmax | Maximum serum concentration | 0 to 36 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | Time to reach Cmax | 0 to 36 week | 
| t1/2 | Terminal half-life | 0 to 36 week | 
| Kel | Terminal elimination rate constant (kel) | 0 to 36 week | 
| Vd/F | Apparent volume of distribution | 0 to 36 week | 
| Cl/F | Apparent clearance | 0 to 36 week | 
| AUEC of sCTX | Area under the effect curve (AUEC) of serum concentration of C-terminal telopeptide of Type 1 collagen (sCTX) | 0 to 36 week | 
| Emax of sCTX | Maximal inhibitory effect (Emax) of sCTX | 0 to 36 week | 
| Incidence of TEAEs(Treatment Emergent Adverse Events) | Experience at least 1 TEAE | 0 to 36 week | 
| Incidence of SAEs(Serious Adverse Events) | Experience at least 1 SAE | 0 to 36 week | 
| Incidence of ADAs (Anti-Drug Antibodies) | Incidence of ADAs to denosumab | 0 to 36 week | 
| Titer of ADAs | Titer of ADAs to denosumab | 0 to 36 week |