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

• ClinicalTrials.gov Identifier: NCT04534582
• Recruitment Status: Not yet recruiting
• First Posted: September 1, 2020
• Last Update Posted: September 1, 2020
• Sponsor: Shanghai Henlius Biotech
• Information provided by (Responsible Party): Shanghai Henlius Biotech

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy Male Volunteers	Drug: HLX14; Drug: EU-Prolia®	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: September 20, 2020
• Estimated Primary Completion Date: December 20, 2020
• Estimated Study Completion Date: August 20, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: HLX14 group; HLX14 are given subcutaneous injection at a single dose of 60 mg.	Drug: HLX14; healthy volunteers receive HLX14 (60mg) once
Active Comparator: EU-Prolia® group; EU-Prolia® are given subcutaneous injection at a single dose of 60 mg.	Drug: EU-Prolia®; healthy volunteers receive EU-Prolia® (60mg) once

Outcome Measures

Primary Outcome Measures :

1. AUC(0-t) [ Time Frame: from 0 to day 183 ]
   Area under the serum concentration-time curve from time 0 to the last concentration-quantifiable time t of denosumab
2. Cmax [ Time Frame: from 0 to day 183 ]
   Maximum serum concentration following administration of denosumab
3. AUC0-inf [ Time Frame: from 0 to day 183 ]
   Area under the serum concentration-time curve from time 0 to infinity

Secondary Outcome Measures :

1. Tmax [ Time Frame: from 0 to day 183 ]
   Time to reach maximum serum concentration following administration
2. CL/F [ Time Frame: from 0 to day 183 ]
   Total clearance
3. λz [ Time Frame: from 0 to day 183 ]
   Apparent terminal elimination rate constant
4. t1/2 [ Time Frame: from 0 to day 183 ]
   Elimination half life
5. Vd/F [ Time Frame: from 0 to day 183 ]
   Apparent volume of distribution
6. AUEC0-t [ Time Frame: from 0 to day 183 ]
   Area under the effect-time curve from time zero to last time of quantifiable concentration of Serum CTX1
7. Imin [ Time Frame: from 0 to day 183 ]
   Minimum observed plasma concentration of Serum CTX1
8. Imax [ Time Frame: from 0 to day 183 ]
   Maximum Percent Inhibition of Serum CTX1
9. Tmin [ Time Frame: from 0 to day 183 ]
   Time to reach Imin of Serum CTX1

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Males aged ≥ 18 and ≤ 65 years;
2. Body weight ≥ 50 kg, body mass index (BMI) = body weight (kg)/body height2 (m2), BMI ≥ 19 and ≤ 26 kg/m2;
3. With no disease history, or with abnormal prior medical history which has no effect on the trial as judged by the physician;
4. Normal or abnormal without clinical significance in physical examination, vital signs, ECG, chest imaging, clinical laboratory test, etc.;
5. 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:

1. 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;
2. 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);
3. With a history of upper respiratory tract infection and other acute infections within 2 weeks prior to screening;
4. 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.
5. With rash, scar, tattoo, etc. at administration site that may affect drug absorption;
6. Blood donation or massive blood loss (> 450 mL) within 3 months prior to screening;
7. Use of any prescription drugs, over-the-counter drugs, vitamin products, or traditional Chinese medicines within 28 days prior to screening;
8. Participation in any drug clinical trials and use of any investigational/comparator drugs within 3 months prior to screening;
9. 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;
10. Use of any biological products or monoclonal antibodies within 6 months prior to screening;
11. 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;
12. With a history of substance abuse or drug abuse, or positive for drug screen;
13. Positive for tobacco screen;
14. With significant changes in physical activity within 6 months prior to screening, or not agree to abstain from strenuous physical exercise during the trial;
15. Positive for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, or treponema pallidum antibody;
16. Abnormal serum calcium level (beyond the laboratory reference range) during the screening;
17. 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.
18. Clinically significant abnormal ECG or QTcF > 450 ms during screening, or with a prior history of clinically significant abnormal ECG;
19. Unwilling to take adequate contraceptive measures from screening to 6 months after the administration of study drugs. See Appendix 2 for specific contraceptive measures;
20. Subjects who, in the opinion of the investigators, are not eligible to participate in this study.

Contacts and Locations

Contacts

Contact: Chaoming Ma, bachelor; 021-33395790; Chaoming_Ma@henlius.com

Sponsors and Collaborators

Shanghai Henlius Biotech

Investigators

• Principal Investigator: Jing Zhang; Huashan Hospital

More Information

• Responsible Party: Shanghai Henlius Biotech
• ClinicalTrials.gov Identifier: NCT04534582
• Other Study ID Numbers: HLX14-001
• First Posted: September 1, 2020
• Last Update Posted: September 1, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Denosumab; Bone Density Conservation Agents; Physiological Effects of Drugs