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

NCT04534582 | Completed Phase 1 FDA Drug

• 1 other identifier: HLX14-001
• Study Type: interventional
• Target: 252
• Locations: 1 country
• Sites: 1

Brief Summary

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®.

Conditions

Healthy Male Volunteers

Outcome Measures

Primary Outcomes (3)

• 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 274

• Cmax

  Maximum serum concentration following administration of denosumab

  from 0 to day 274

• AUC0-inf

  Area under the serum concentration-time curve from time 0 to infinity

  from 0 to day 274

Secondary Outcomes (12)

• Tmax

  from 0 to day 274

• CL/F

  from 0 to day 274

• λz

  from 0 to day 274

• t1/2

  from 0 to day 274

• Vd/F

  from 0 to day 274

Other Outcomes (7)

• AEs and SAEs

  from 0 to day 274

• Physical examination

  from 0 to day 274

• Vital signs

  from 0 to day 274

Study Arms (6)

Part I: HLX14 group

EXPERIMENTAL

Part I: HLX14 are given subcutaneous injection at a single dose of 60 mg.

Drug: HLX14

Part I: EU-Prolia® group

ACTIVE COMPARATOR

Part I: EU-Prolia® are given subcutaneous injection at a single dose of 60 mg.

Drug: EU-Prolia®

Part II: HLX14 group

EXPERIMENTAL

Part II: HLX14 are given subcutaneous injection at a single dose of 60 mg.

Drug: HLX14

Part II: EU-Prolia® group

ACTIVE COMPARATOR

Part II: EU-Prolia® are given subcutaneous injection at a single dose of 60 mg.

Drug: EU-Prolia®

Part II: US-Prolia® group

ACTIVE COMPARATOR

Part II: US-Prolia® are given subcutaneous injection at a single dose of 60 mg.

Drug: US-Prolia®

Part II: CN-Prolia® group

ACTIVE COMPARATOR

Part II: CN-Prolia® are given subcutaneous injection at a single dose of 60 mg.

Drug: CN-Prolia®

Interventions

HLX14 DRUG

healthy volunteers receive HLX14 (60mg) once

Part I: HLX14 group; Part II: HLX14 group

EU-Prolia® DRUG

healthy volunteers receive EU-Prolia® (60mg) once

Part I: EU-Prolia® group; Part II: EU-Prolia® group

US-Prolia® DRUG

healthy volunteers receive US-Prolia® (60mg) once

Part II: US-Prolia® group

CN-Prolia® DRUG

healthy volunteers receive CN-Prolia® (60mg) once

Part II: CN-Prolia® group

Eligibility Criteria

• Age: 28 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males aged\> 28 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.

You may not qualify if:

• 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, cardiovascular and cerebrovascular diseases, or any condition that may affect bone metabolism);
• 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.
• Occurrence of fracture or bone-related surgery within 6 months prior to screening;
• 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 (OTC) 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 the following drugs affecting bone metabolism:
• Administration history of denosumab or its biosimilar products, romosozumab or its biosimilar products, cathepsin K inhibitors, diphosphonates, fluorides, or stronitum;
• Administration of the following within 12 months before screening: parathyroid hormone or its derivatives, hormone replacement therapy (HRT), selective estrogen receptor modulators (SERM), tibolone, anabolic steroids, testosterone, androgen, and gonadotropin-releasing hormone agonists (GnRH-a);
• Administration of any prescription drug or OTC drug within 6 months or 10 half-lives of drug elimination (whichever is the longer) before screening that may have impact on the objectives of the study at the discretion of the investigator, including but not limited to heparin, warfarin, anticonvulsants (excluding benzodiazepine), systemic ketoconazole, adrenocorticotropic hormone (ACTH), cinacalcet, aluminum, lithium, protease inhibitors (PI), methotrexate (MTX), calcitonin, calcitriol, diuretics, and glucocorticoids for oral administration or injection (daily administration of ≥ 5 mg prednisone or equivalent drugs for more than 10 days);
• Use of any biological products (excluding vaccine) or monoclonal antibodies within 6 months prior to screening;

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (1)

Huashan Hospital，Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Related Publications (2)

• Li N, Chu N, Zhu L, Wu X, Wei Q, Wang J, Hu X, Yu H, Wang Q, Yuan W, Huang K, Zhang J. Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 versus reference denosumab in healthy males: A randomized phase I study. Clin Transl Sci. 2024 Dec;17(12):e70089. doi: 10.1111/cts.70089.

  PMID: 39700054 RESULT

• American Society for Clinical Pharmacology and Therapeutics. Clin Pharmacol Ther. 2022 Mar;111 Suppl 1:S5-S80. doi: 10.1002/cpt.2521. No abstract available.

  PMID: 35132630 RESULT

Study Officials

• Jing Zhang, Doctor

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part I: open label Part II: masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2020
• First Posted: September 1, 2020
• Study Start: November 3, 2020
• Primary Completion: September 12, 2023
• Study Completion: September 12, 2023
• Last Updated: January 20, 2025

Record last verified: 2024-03

Locations

CN (1)