AVT03 With Xgeva in Healthy Male Subjects

Study Overview
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Brief Summary
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This study has been designed as a randomized, double-blind, parallel-group study and in healthy adult male subjects of age 28 years to 55 years old. The study will assess the PK, safety and tolerability of AVT03 compared to US-Xgeva when administered as a single 120 mg SC dose

Detailed Description
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The study will consist of a 28 days( 4 week) screening period, a 196 day (28 weeks) treatment and assessment period, and an End of Study (EOS) visit on week 32 on Day 196. Subjects will undertake a screening visit between Day -28 and Day -1 to determine their eligibility for the study. Subjects who meet the eligibility criteria will be admitted to the study site on the day prior to dosing (Day -1), during which their continued eligibility will be assessed up to Day 1 prior to dosing. On Day 1, eligible subjects will be randomized and will receive a single dose of 120mg AVT03 or 120mg Xgeva as subcutaneous injection.

Official Title
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A Randomized, Double-blind, Parallel Design, Single Dose, 2-arm Study Comparing the Pharmacokinetic, Safety and Immunogenicity Profiles of AVT03 and US-Xgeva® in Healthy Male Subjects

Conditions
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This is a Phase Study Conducted in Healthy Volunteers

Intervention / Treatment
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* Biological: Denosumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Male subjects who are 28 to 55 years old, inclusive, at the time of signing the ICF. Have a body weight of 50.0 to 90.0 kg (inclusive) and body mass index of 17.0 to 32. Subjects in Japanese cohorts must be born in Japan, holding a Japanese passport. Not living outside Japan for more than 5 years (from the date of informed consent) and have all 4 grandparents Japanese, as confirmed by interview. kg/m2 at Screening and Day -1 Exclusion Criteria: 1. Evidence of clinically relevant pathology, especially prior diagnosis of bone disease, or any uncontrolled condition that will affect bone metabolism such as, but not limited to: osteoporosis, osteogenesis imperfecta, hyperparathyroidism,, non-controlled hyperthyroidism osteomalacia, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, current flare-up of osteoarthritis and/or gout, active malignancy, renal disease (defined as glomerular filtration rate <45 mL/min), Paget's disease of the bone, malabsorption syndrome. 2. Have osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (e.g., tooth extraction, dental implants, oral surgery) within 6 months prior to Day 1 or intend to undergo such procedures during the study period, poor oral hygiene, periodontal, and/or pre-existing dental disease. 3. Have bone fractures, presence of active healing fractures, or recent bone fracture within 6 months prior to Day -1.

Ages Eligible for Study
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Minimum Age: 28 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm AVT03 120mg<br>AVT03 (denosumab) is the proposed biosimilar for Xgeva (denosumab). Subjects in this arm will receive a single 120mg dose of AVT03 (denosumab) as a subcutaneous injection | Biological: Denosumab<br>* AVT03 (denosumab) or Xgeva (denosumab) will be given as 1 time subcutaneous injection)<br>* Other names: Xgeva, AVT03, Biosimilar Denosumab;|
| Active Comparator: Active Comparator Xgeva 120mg<br>Xgeva (denosumab) is the proposed active comparator for AVT03 (denosumab). Subjects in this arm will receive a single 120mg dose of Xgeva (denosumab) as a subcutaneous injection | Biological: Denosumab<br>* AVT03 (denosumab) or Xgeva (denosumab) will be given as 1 time subcutaneous injection)<br>* Other names: Xgeva, AVT03, Biosimilar Denosumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Co-primary PK endpoint_Cmax: maximum serum concentration | Venous blood samples will be collected for measurement serum concentration of AVT03 and Xgeva | Day 1(week 1) to Day 196 (week 28) | 
| Co-primary PK endpoint_AUC0-t: area under the serum concentration-time curve up to time t, where t is the last time point with a concentration above the lower limit of quantitation | Venous blood samples will be collected for measurement of Area under serum concentration-time curve (AUC 0-t) AVT03 and Xgeva | Day 1(week 1) to Day 196 (week 28) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Denosumab, Healthy Volunteers