Comparing of the PK, PD, Safety and Immunogenicity of HS-20090 and Xgeva® in Healthy Adults

Study Overview
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Brief Summary
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A Dual-center , Randomized, double-blinded and Parallel-controlled Study to Assess the Pharmacokinetic, pharmacodynamics, Safety and Immunogenicity of HS-20090 Injection and Xgeva® in Healthy Adults

Detailed Description
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This is a phase I, dual-center, randomized, double-blind and parallel group clinical trial . The primary objective is to assess the pharmacokinetic similarity of single subcutaneously injection of HS-20090 or Xgeva® in healthy volunteers. The secondary objectives are to assess the Clinical safety and immunogenicity similarity of single subcutaneously injection of HS-20090 or Xgeva® in healthy volunteers. Meanwhile, observing the pharmacodynamic similarity of HS-20090 to Xgeva® preliminarily.

Official Title
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A Dual-center, Randomized, Double-blinded and Parallel-controlled Study to Assess the Pharmacokinetic, Pharmacodynamics, Safety and Immunogenicity of HS-20090 Injection and Xgeva® in Healthy Adults

Conditions
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Healthy

Intervention / Treatment
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* Drug: HS-20090
* Drug: Xgeva®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign the informed consent form and fully understand the test content, process and possible adverse reactions, and be able to complete the study according to the test plan requirements; Healthy males, Aged ≥18 years and ≤50 years old(including the boundary value); Subjects weighing ≥ 55 kg and ≤ 75 kg (weight difference in a single center is controlled within 10 kg), with a BMI between 19.0 and 26.0 kg/m2 (BMI = weight (kg)/height2 (m2)) (including borderline values). The subject agrees to use effective contraception for at least 6 months from the screening date until after study dosing, and has no plans to have children or donate sperm within 6 months; Physical examination, vital signs, laboratory examination, chest X-ray, B-ultrasound and electrocardiogram are normal, or the above tests are abnormal without clinically significance and have no effect on the test as judged by the investigator; ECG examination: corrected QT interval (QTcF) < 450 ms. Exclusion Criteria: Occurred or suffering from osteomyelitis or ONJ (OsteoNecrosis of the Jaw) previously; The dental or jaw disease that is active, requiring oral surgery; or planned for invasive dental surgery during the study; or dental or oral surgery wounds have not healed; Subjects with any previous or current clinically serious diseases such as circulatory, endocrine, neurological, digestive, respiratory, genitourinary, hematological, immunological, psychiatric, and metabolic abnormalities or any other diseases that can interfere with the study results. Positive screening for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, Acquired Immune Deficiency Syndrome (AIDS) antibodies, and syphilis spirochete antibodies. Abnormal blood calcium: current hypocalcemia or hypercalcemia. Serum calcium outside the normal laboratory range; (Subjects should not apply calcium supplements for at least 8 hours prior to drawing blood for serum calcium screening assays.) previous use of RANKL inhibitors or osteoclastogenesis inhibitory factor. The subject is participating in another clinical study, or the first dose was administered less than 3 months after the last dose of the previous clinical study (or 5 half-lives of the study drug, whichever is longer). Average daily smoking ≥ 5 cigarettes in the 3 months prior to randomization. Prior history of alcohol abuse (14 units of alcohol per week: 1 unit = 360 mL of beer or 45 mL of spirits at 40% alcohol or 150 mL of wine), substance abuse or drug use. Positive substance abuse screening or/and alcohol breath test screening prior to study administration. Subjects who have donated blood within 3 months prior to administration, or have lost more than 400 ml of blood, or are scheduled to donate blood within 6 months. Subjects who have had a significant change in physical status within 6 months prior to administration, or who have been performing strenuous exercise. Subjects who, in the opinion of the investigator, have any factors that make participation in this trial inadvisable.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HS-20090<br>Subcutaneously injection of HS-20090 (120mg/1.7mL) once on the first day | Drug: HS-20090<br>* A human IgG2 monoclonal antibody with affinity and specificity for human RANKL<br>* Other names: Recombinant human anti-RANKL monoclonal antibody injection;|
| Active Comparator: Xgeva®<br>Subcutaneously injection of Xgeva® (120mg/1.7mL) once on the first day | Drug: Xgeva®<br>* Xgeva® injection (120mg) by subcutaneous injection once on the first day subcutaneous injection of 120 mg (1.7 ml)only once<br>* Other names: Denosumab Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-∞ | The area under the curve from time 0 extrapolated to infinite time | 155days | 
| Cmax | Maximum concentration | 155days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t | Area under the plasma concentration-time curve | 155days | 
| Tmax | Time to reach Cmax | 155days | 
| t1/2z | Terminal half-life | 155days | 
| Vz/F | Apparent volume of distribution | 155days | 
| CLz/F | Apparent clearance | 155days | 
| Serum type 1 C-telopeptide(CTX1) | explore the pharmacodynamic profile by detecting the serum concentration of CTX1 | 155days | 
| Imin | The minimum observed concentration | 155days | 
| TEmax | Time to reach the maximum inhibition rate | 155days | 
| Emax | Maximum observed inhibition rate | 155days | 
| AUEC0-t | Area under the plasma effect-time curve from time zero to last time of quantifiable concentrationthe | 155days | 
| Adverse events(AE) | The adverse medical events that occur after the clinical trial subjects receive the test drug do not necessarily have a causal relationship with the treatment. | 155days | 
| Antidrug antibody(ADA): | percentage of subjects positive for antidrug antibody | 155days | 
| Neutralizing antibody(Nab) | percentage of subjects positive for Nab | 155days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HS-20090, Pharmacokinetic, pharmacodynamics, Safety, Immunogenicity