Pharmacokinetic, Safety and Immunogenicity Phase I Study of HLX14 Versus Prolia® in Healthy Male Subjects

Study Overview
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Brief Summary
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Part I of the study： This is a randomised, single-dose, subcutaneous injection, parallel study designed to compare the PK of HLX14 and EU-sourced Prolia® in healthy Chinese adult male subjects, and to assess the safety, tolerability, and immunogenicity of these 2 drugs. Part II of the study： This is a randomised, double-blind, four-arm, single-dose, subcutaneous injection, parallel-controlled study to evaluate the PK, PD, safety, tolerability, and immunogenicity between-group following a single subcutaneous injection of HLX14 or US, EU, CN-sourced Prolia®.

Official Title
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A Randomised, Parallel, Single-Dose, Subcutaneous Injection, Phase I Clinical Study Of HLX14 Versus Prolia® (Denosumab) In Chinese Healthy Adult Male Subjects For Comparison In Pharmacokinetic Characteristics, Safety, And Immunogenicity

Conditions
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Healthy Male Volunteers

Intervention / Treatment
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* Drug: HLX14
* Drug: EU-Prolia®
* Drug: US-Prolia®
* Drug: CN-Prolia®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males aged ≥ 18 and ≤ 65 years; Body weight ≥ 50 kg, body mass index (BMI) = body weight (kg)/body height2 (m2), BMI ≥ 19 and ≤ 26 kg/m2; With no disease history, or with abnormal prior medical history which has no effect on the trial as judged by the physician; Normal or abnormal without clinical significance in physical examination, vital signs, ECG, chest imaging, clinical laboratory test, etc.; Before the trial, sign the informed consent form (ICF) and have a full understanding of trial content, process, and possible adverse events (AEs); be able to complete the study as per protocol requirements. Exclusion Criteria: With a history of allergy to study drugs, calcium, and/or vitamin D, or with a history of allergy to drugs or others not suitable for participating in this study as judged by the investigators; With the following clinically significant diseases (including but not limited to digestive system, kidney diseases, liver diseases, nervous diseases, blood system, endocrine system, tumor, respiratory system, immune diseases, mental diseases, or cardiovascular and cerebrovascular diseases); With a history of upper respiratory tract infection and other acute infections within 2 weeks prior to screening; Occurred or suffering from osteomyelitis or ONJ (Osteonecrosis of the jaw) previously. The dental or jaw disease that is active, requiring oral surgery; or dental or oral surgery wounds have not healed; or planned for invasive dental surgery during the study. With rash, scar, tattoo, etc. at administration site that may affect drug absorption; Blood donation or massive blood loss (> 450 mL) within 3 months prior to screening; Use of any prescription drugs, over-the-counter drugs, vitamin products, or traditional Chinese medicines within 28 days prior to screening; Participation in any drug clinical trials and use of any investigational/comparator drugs within 3 months prior to screening; Administration of drugs affecting bone metabolism within 6 months before participating in this study, including but not limited to: bisphosphonates, fluoride, calcitonin, strontium, parathyroid hormone or its derivatives, vitamin D supplements (> 1000 IU/day), glucocorticoids, anabolic steroids, calcitriol, and diuretics; Use of any biological products or monoclonal antibodies within 6 months prior to screening; With a history of alcohol abuse (14 units of alcohol per week: 1 unit = 285 mL of beer, 25 mL of spirit, or 100 mL of wine), or positive for alcohol breath test; With a history of substance abuse or drug abuse, or positive for drug screen; Positive for tobacco screen; With significant changes in physical activity within 6 months prior to screening, or not agree to abstain from strenuous physical exercise during the trial; Positive for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, or treponema pallidum antibody; Abnormal serum calcium level (beyond the laboratory reference range) during the screening; Body temperature > 37.5 °C; and/or sitting systolic blood pressure (SBP) > 140 mmHg or < 90 mmHg, and/or diastolic blood pressure (DBP) > 90 mmHg or < 50 mmHg; and/or pulse rate > 100 beats/min or < 50 beats/min during the screening. Clinically significant abnormal ECG or QTcF > 450 ms during screening, or with a prior history of clinically significant abnormal ECG; Unwilling to take adequate contraceptive measures from screening to 6 months after the administration of study drugs. See Appendix 2 for specific contraceptive measures; Subjects who, in the opinion of the investigators, are not eligible to participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HLX14 group<br>HLX14 are given subcutaneous injection at a single dose of 60 mg. | Drug: HLX14<br>* healthy volunteers receive HLX14 (60mg) once<br>|
| Active Comparator: EU-Prolia® group<br>EU-Prolia® are given subcutaneous injection at a single dose of 60 mg. | Drug: EU-Prolia®<br>* healthy volunteers receive EU-Prolia® (60mg) once<br>|
| Active Comparator: US-Prolia® group<br>US-Prolia® are given subcutaneous injection at a single dose of 60 mg. | Drug: US-Prolia®<br>* healthy volunteers receive US-Prolia® (60mg) once<br>|
| Active Comparator: CN-Prolia® group<br>CN-Prolia® are given subcutaneous injection at a single dose of 60 mg. | Drug: CN-Prolia®<br>* healthy volunteers receive CN-Prolia® (60mg) once<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-t) | Area under the serum concentration-time curve from time 0 to the last concentration-quantifiable time t of denosumab | from 0 to day 183 | 
| Cmax | Maximum serum concentration following administration of denosumab | from 0 to day 183 | 
| AUC0-inf | Area under the serum concentration-time curve from time 0 to infinity | from 0 to day 183 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | Time to reach maximum serum concentration following administration | from 0 to day 183 | 
| CL/F | Total clearance | from 0 to day 183 | 
| λz | Apparent terminal elimination rate constant | from 0 to day 183 | 
| t1/2 | Elimination half life | from 0 to day 183 | 
| Vd/F | Apparent volume of distribution | from 0 to day 183 | 
| AUEC0-t | Area under the effect-time curve from time zero to last time of quantifiable concentration of Serum CTX1 | from 0 to day 183 | 
| Imin | Minimum observed plasma concentration of Serum CTX1 | from 0 to day 183 | 
| Imax | Maximum Percent Inhibition of Serum CTX1 | from 0 to day 183 | 
| Tmin | Time to reach Imin of Serum CTX1 | from 0 to day 183 |