A Study to Evaluate LY01011 and Xgeva® in Healthy Adults

Study Overview
=================
Brief Summary
-----------------
A randomized, double-blind, single-dose, parallel-group study to compare the pharmacokinetics, pharmacodynamics, safety and immunogenicity of LY01011 and Xgeva® in healthy adults

Detailed Description
-----------------
This is a phase I, randomized, double-blind, single-dose, parallel-group clinical trial . The primary objective is to assess the pharmacokinetic similarity of single and subcutaneous injections of LY01011 or Xgeva® in healthy volunteers. The secondary objective are to compare the safety, tolerability, immunogenicity and pharmacodynamics of single and subcutaneous injections of LY01011 or Xgeva® in healthy volunteers.

Official Title
-----------------
A Randomized, Double-blind, Single-dose, Parallel-group Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of LY01011 and Xgeva® in Healthy Adults

Conditions
-----------------
Healthy Adults

Intervention / Treatment
-----------------
* Drug: LY01011
* Drug: Xgeva 120 MG in 1.7 ML Injection


Participation Criteria
=================
Eligibility Criteria
-----------------
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 During the study period, the subjects and partners agreed to use reliable contraceptive measures Aged ≥18 years or ≤50 years, male or female (including the boundary value) Male body weight≥50kg，female body weight≥45kg，and 18.0≤BMI≤28.0 kg/m2 Clinical laboratory examination, chest X-ray, abdominal B-ultrasound, electrocardiogram, physical examination, vital signs and various examinations are normal or abnormal without clinical significance at screening Exclusion Criteria: Subjects are suffering from or have had osteomyelitis or osteonecrosis of the Jaw, or plan to have invasive dental or maxillofacial surgery during the study, or dental or oral surgery wounds unhealed Have fractures in past six months The medicines that may affect bone turnover are used before screening or planned to use in the study period , including but not limited : Denosumab, bisphosphonates or fluorides were used in past 12 months; Contraceptives with hormone were used in past 6 months，Hormone replacement therapy（tibolone、hormone、selective estrogen receptor modulators）Aromatase inhibitors, calcitonin, strontium salt, parathyroid hormone (or derivative), vitamin D supplement，Anabolic steroids, systemic glucocorticoids, calcitriol or analogues, diuretics, anticonvulsant drugs；Inhalation or local use of glucocorticoids within 2 weeks Hypocalcemia or hypercalcemia，or serum calcium calibrated by serum albumin was not within the normal range Subjects with allergic constitution (allergic to more than two drugs or food) or known to be allergic to the ingredients of the investigational product Donated whole blood, blood component, or massive hemorrhage （>450ml）three months before screening Use of any vaccines in 4 weeks of initiation of study therapy Use Rx or OTC drugs or nutritional health products or herbal supplements within 14 days before the screening Have been playing strenuous sports in 2 weeks before screening; or other factors affecting drug absorption, distribution, metabolism, excretion The average daily smoking amount is more than 5 cigarettes per day during three months before screening; History of drug abuse or alcohol abuse (drank more than 14 units / week of alcohol: 1 unit =285ml beer, 25ml spirits or 100ml Wine)； History of drug abuse within 5 years prior to screening, or urine drug screening test was positive； other clinically significant diseases (such as neuropsychiatric system, cardiovascular system, urinary system, digestive system, respiratory system, metabolic endocrine system, blood system, skin diseases, immune diseases, tumors, etc.) Any of HBsAg, HCV-Ab, Anti-HIV, TP-Ab was positive Acute disease or combination of medication from the screening to the study before the use of investigational product , Take any alcoholic product within 48 hours before using the investigational product Participation in another clinical trial within 3 months prior to enrollment Anticipated of partner pregnancy during the study. Other conditions that the investigator thinks unsuitable in this study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY01011<br>LY01011 injection (120mg) by subcutaneous injection once on the first day subcutaneous injection of 120 mg (1.7 ml)only once | Drug: LY01011<br>* LY01011 injection (120mg) by subcutaneous injection once on the first day subcutaneous injection of 120 mg (1.7 ml)only once<br>* Other names: subcutaneous injection of 120 mg (1.7 ml);|
| Active Comparator: Xgeva®<br>Xgeva® injection (120mg) by subcutaneous injection once on the first day subcutaneous injection of 120 mg (1.7 ml)only once | Drug: Xgeva 120 MG in 1.7 ML Injection<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: subcutaneous injection of 120 mg (1.7 ml);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Assess the Cmax similarity of single and subcutaneous injections of LY01011 or Xgeva® in healthy volunteers | 168 days | 
| AUC0-t | Assess the AUC0-t similarity of single and subcutaneous injections of LY01011 or Xgeva® in healthy volunteers | 168 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AE | Number of patients with treatment related adverse events assessed by change from baseline | 168 days | 
| ADA | Number of patients with ADA | 168 days | 
| Nab | Number of patients with Nab | 168 days | 
| AUC0-∞ | Assess area under the Curve (AUC) | 168 days | 
| Tmax | Assess the Tmax | 168 days | 
| CL/F | Assess the CL/F | 168 days | 
| λz | Assess the λz | 168 days | 
| t1/2 | Assess the t1/2 | 168 days | 
| Vd/F | Assess the Vd/F | 168 days | 
| AUEC0-t of CTX-1 | Assess the AUEC0-t of CTX-1 | 168 days | 
| Emax | Assess the Emax of CTX-1 | 168 days | 
| TEmax | Assess the TEmax of CTX-1 | 168 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Compare, Pharmacokinetics, Pharmacodynamics, Safety, Immunogenicity, LY01011, Xgeva®, Healthy adults