Healthy Male VolunteersPhase 1NCT04534582
Pharmacokinetic, Safety and Immunogenicity Phase I Study of HLX14 Versus Prolia® in Healthy Male Subjects
A Phase 1 study testing HLX14, EU-Prolia® and US-Prolia® in people with Healthy Male Volunteers, run by Shanghai Henlius Biotech at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 28 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Male Volunteers
- What is being tested?
- HLX14, EU-Prolia® and US-Prolia®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 252 participants
- Where
- 1 siteChina
- Study dates
- 3 Nov 2020to 12 Sep 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 28 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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;
- Vaccination within 1 month 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 (TPPA);
- Abnormal serum calcium level (beyond the laboratory reference range) during the screening;
- Ear temperature > 37.5 °C during the screening period; 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 during the study.
- Subjects who, in the opinion of the investigators, are not eligible to participate in this study.
Trial locations and contacts
1 site in 1 country.
China1 site
Huashan Hospital，Fudan University
Shanghai, Shanghai Municipality, 200040
About this study
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
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
- Being tested
- HLX14, EU-Prolia®, US-Prolia®, CN-Prolia®
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HLX14Drug
healthy volunteers receive HLX14 (60mg) once
EU-Prolia®Drug
healthy volunteers receive EU-Prolia® (60mg) once
US-Prolia®Drug
healthy volunteers receive US-Prolia® (60mg) once
CN-Prolia®Drug
healthy volunteers receive CN-Prolia® (60mg) once
| Study group | Role | What they receive |
|---|---|---|
| Part I: HLX14 group | Experimental | Part I: HLX14 are given subcutaneous injection at a single dose of 60 mg. Receives: Drug: HLX14 |
| Part I: EU-Prolia® group | Active comparator | Part I: EU-Prolia® are given subcutaneous injection at a single dose of 60 mg. Receives: Drug: EU-Prolia® |
| Part II: HLX14 group | Experimental | Part II: HLX14 are given subcutaneous injection at a single dose of 60 mg. Receives: Drug: HLX14 |
| Part II: EU-Prolia® group | Active comparator | Part II: EU-Prolia® are given subcutaneous injection at a single dose of 60 mg. Receives: 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. Receives: 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. Receives: Drug: CN-Prolia® |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC(0-t)
Area under the serum concentration-time curve from time 0 to the last concentration-quantifiable time t of denosumab
Measured: from 0 to day 274
Cmax
Maximum serum concentration following administration of denosumab
Measured: from 0 to day 274
AUC0-inf
Area under the serum concentration-time curve from time 0 to infinity
Measured: from 0 to day 274
Secondary outcomes (12)
Tmax
Time to reach maximum serum concentration following administration
Measured: from 0 to day 274
CL/F
Total clearance
Measured: from 0 to day 274
λz
Apparent terminal elimination rate constant
Measured: from 0 to day 274
t1/2
Elimination half life
Measured: from 0 to day 274
Vd/F
Apparent volume of distribution
Measured: from 0 to day 274
%AUCex
Area extrapolated from time to infinity as a percentage of total AUC0-inf
Measured: from 0 to day 274
MRT
Mean residence time
Measured: from 0 to day 274
AUC0-28d and AUC0-112d
Area under the drug concentration-time curve from day 0 to day 28 (4 weeks) and from day 0 to day 112 (16 weeks)
Measured: from 0 to day 112
AUEC0-t
Area under the effect-time curve from time zero to last time of quantifiable concentration of serum CTX1
Measured: from 0 to day 274
Imin
Minimum observed concentration of serum CTX1
Measured: from 0 to day 274
Imax
Maximum percent inhibition of serum CTX1
Measured: from 0 to day 274
Tmin
Time to reach Imin of serum CTX1
Measured: from 0 to day 274
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2020
- Study start3 Nov 2020
- Primary completion12 Sep 2023
- Study completion12 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Healthy Male VolunteersStudies of the same condition, open and under way.
- More trials run by Shanghai Henlius BiotechThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 252 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai Henlius Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jing Zhang, Doctor, Principal investigator, Huashan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04534582
- Sponsor's protocol ID
- HLX14-001
- Status last verified
- Mar 2024
- First submitted
- 27 Aug 2020
- Last updated
- 20 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 39700054American Society for Clinical Pharmacology and Therapeutics. Clin Pharmacol Ther. 2022 Mar;111 Suppl 1:S5-S80. doi: 10.1002/cpt.2521. No abstract available.
PubMed 35132630
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04534582
- Acronym / sponsor ID
- HLX14-001
- Conditions
- Healthy Male Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 252 participants (actual)
- Lead sponsor
- Shanghai Henlius BiotechIndustry (pharma, biotech, devices)
- Study start
- 3 Nov 2020 (actual)
- Primary completion
- 12 Sep 2023 (actual)
- Study completion
- 12 Sep 2023 (actual)
- First posted
- 1 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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®.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part I: HLX14 group | Experimental | Drug: HLX14Part I: HLX14 are given subcutaneous injection at a single dose of 60 mg. |
| Part I: EU-Prolia® group | Active comparator | Drug: EU-Prolia®Part I: EU-Prolia® are given subcutaneous injection at a single dose of 60 mg. |
| Part II: HLX14 group | Experimental | Drug: HLX14Part II: HLX14 are given subcutaneous injection at a single dose of 60 mg. |
| Part II: EU-Prolia® group | Active comparator | Drug: EU-Prolia®Part II: EU-Prolia® are given subcutaneous injection at a single dose of 60 mg. |
| Part II: US-Prolia® group | Active comparator | Drug: US-Prolia®Part II: US-Prolia® are given subcutaneous injection at a single dose of 60 mg. |
| Part II: CN-Prolia® group | Active comparator | Drug: CN-Prolia®Part II: CN-Prolia® are given subcutaneous injection at a single dose of 60 mg. |
Who may qualify
- Ages
- 28 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HLX14healthy volunteers receive HLX14 (60mg) once | Drug | Part I: HLX14 group, Part II: HLX14 group |
| EU-Prolia®healthy volunteers receive EU-Prolia® (60mg) once | Drug | Part I: EU-Prolia® group, Part II: EU-Prolia® group |
| US-Prolia®healthy volunteers receive US-Prolia® (60mg) once | Drug | Part II: US-Prolia® group |
| CN-Prolia®healthy volunteers receive CN-Prolia® (60mg) once | Drug | Part II: CN-Prolia® group |
Primary outcome
AUC(0-t)
Time frame: from 0 to day 274
Area under the serum concentration-time curve from time 0 to the last concentration-quantifiable time t of denosumab
Cmax
Time frame: from 0 to day 274
Maximum serum concentration following administration of denosumab
AUC0-inf
Time frame: from 0 to day 274
Area under the serum concentration-time curve from time 0 to infinity
12 secondary outcomes
Tmax
Time frame: from 0 to day 274
CL/F
Time frame: from 0 to day 274
λz
Time frame: from 0 to day 274
t1/2
Time frame: from 0 to day 274
Vd/F
Time frame: from 0 to day 274
%AUCex
Time frame: from 0 to day 274
MRT
Time frame: from 0 to day 274
AUC0-28d and AUC0-112d
Time frame: from 0 to day 112
AUEC0-t
Time frame: from 0 to day 274
Imin
Time frame: from 0 to day 274
Imax
Time frame: from 0 to day 274
Tmin
Time frame: from 0 to day 274
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2025.
- Results publication: PubMed 39700054Li 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.
- Results publication: PubMed 35132630American Society for Clinical Pharmacology and Therapeutics. Clin Pharmacol Ther. 2022 Mar;111 Suppl 1:S5-S80. doi: 10.1002/cpt.2521. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jing Zhang, Doctor principal investigator
Huashan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HLX14, EU-Prolia® and US-Prolia® in people with Healthy Male Volunteers, run by Shanghai Henlius Biotech at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC(0-t) (time frame: from 0 to day 274). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04534582, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2025.