AVT03 With Prolia 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, PD, safety and tolerability of AVT03 compared to Prolia when administered as a single 60 mg SC dose

Detailed Description
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The study will consist of a 4 week screening period, a 252 day (36 weeks) treatment and assessment period, and an End of Study (EOS) visit on week 36 on Day 252. 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 60mg AVT03 or 60mg Prolia as subcutaneous injection.

Official Title
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A Randomized, Double-blind, Single-dose, Parallel-group Design, 2 Arm Study Comparing the Pharmacokinetic, Pharmacodynamic, Safety, Tolerability, and Immunogenicity Profiles of AVT03 and Prolia® in Healthy Male Subjects

Conditions
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Healthy Male Subjects

Intervention / Treatment
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* Biological: Denosumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects who are 28 to 55 years old, inclusive Have a body weight of 50.0 to 90.0 kg (inclusive) and body mass index (BMI) of 17.0 to 32.0 kg/m2 (inclusive)at Screening and Day -1 Medical history without evidence of a clinically significant disorder, condition, or disease that, in the opinion of the Investigator, would pose a risk to subject safety Exclusion Criteria: Any 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, 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 <45 mL/min], Paget's disease of the bone, recent bone fracture [within 6 months], and malabsorption syndrome) Have osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (eg, 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 Have bone fractures within 6 months prior to Day -1. Have a history of immunodeficiency Those with skin allergies, or are susceptible to autoinflammatory skin disorders, or prone to the development of allergic skin inflammation Abnormal serum calcium: current hypocalcemia or hypercalcemia at Screening. Serum calcium levels must be within reference ranges. Known vitamin D deficiency (25[OH]D levels <15 ng/mL [37.5 nmol/L]) after supplementation at Screening Known intolerance to calcium or vitamin D supplements Any current active infections, including localized infections, or any recent history (within 1 week prior to IP administration) of active infections, cough or fever, or a history of recurrent or chronic infections Known or suspected clinically relevant drug hypersensitivity to denosumab or any of its constituents, which in the opinion of the Investigator, contraindicates the subject's participation History or presence of malignancy (except for successfully treated basal or squamous cell carcinoma) Recent history of major surgery within 3 months prior to Day -1 and/or plan to have an operation (including invasive dental procedures) during the study period Receipt of any investigational agent or drug within 8 weeks or 5 half-lives of that drug, whichever is longer, prior to IP administration in the current study Previous treatment with denosumab (Prolia/Xgeva or its biosimilars) Other criteria may apply

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
Interventional Model Description: Arm 1: AVT03 Arm 2: Prolia
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVT03 Arm<br>AVT03 (denosumab) is the proposed biosimilar for Prolia (denosumab). Subjects in this arm will receive a single 60mg dose of AVT03 (denosumab) as a subcutaneous injection. | Biological: Denosumab<br>* AVT03 (denosumab) or Prolia (denosumab) will be given as 1 time subcutaneous injection)<br>* Other names: Prolia, AVT03, Biosimilar Denosumab;|
| Active Comparator: Prolia Arm<br>Prolia(denosumab) is the proposed comparator for AVT03 (denosumab). Subjects in this arm will receive a single 60mg dose of Prolia (denosumab) as a subcutaneous injection. | Biological: Denosumab<br>* AVT03 (denosumab) or Prolia (denosumab) will be given as 1 time subcutaneous injection)<br>* Other names: Prolia, AVT03, Biosimilar Denosumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the serum concentration-(AUC0-t) from day 0 to day 252 | Venous blood samples will be collected for measurement of Area under serum concentration-time curve (AUC 0-t) AVT03 and Prolia | Day 1(week 1) to Day 252 (week 36) | 
| Maximum serum concentration Cmax | Venous blood samples will be collected for measurement of maximum serum concentration of AVT03 and Prolia | Day 1(week 1) to Day 252 (week 36) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PD_AUC0-last for CTX-1 (% inhibition)C terminal telopeptide of type 1 collagen) | Venous blood samples will be collected for measurement of serum concentration of AVT03 and Prolia | Day 1(week 1) to Day 252 (week 36) | 
| Area under the concentration-time curve AUC0-24 | Venous blood samples will be collected for measurement of serum concentration of AVT03 and Prolia | Day 1(week 1) to Day 162 (week 24)] | 
| Adverse Events | Adverse events will be coded using MedDRA and grouped by system organ class and preferred term and summarised, by treatment group at the time of onset of the AE. The summary tables will present the number and percentage of total subjects and number of events, by system organ class and by preferred term. Injection related reactions will be listed and summarized by reaction using frequency counts and percentage, by treatment group. | Screening to Day 252 (week 36) | 

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