Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity of Biosimilar Denosumab With Prolia® in Healthy Adult Male Volunteers

Healthy Male Subjects Clinical Trial

Official title:

A Randomized, Double-blind, Three-arm, Parallel-group, Single-dose Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity of Denosumab (ENZ215, EU-sourced Prolia®, and US-sourced Prolia®) in Healthy Adult Male Volunteers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05245669
• Other study ID #: ALK22/ENZ215-DEN1
• Secondary ID: 2021-004177-32
• Status: Recruiting
• Phase: Phase 1
• Start date: February 7, 2022
• Est. completion date: May 2024

Study information

• Verified date: May 2023
• Source: Enzene Biosciences Ltd.
• Contact: Dr. Harish Shandilya
• Phone: +9102067184202
• Email: harish.shandilya[@]enzene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, three-arm, parallel-group, single-dose study to demonstrate bioequivalence of ENZ215 and EU- and US-sourced Prolia after a single 60-mg dose administered subcutaneously in healthy adult male volunteers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 207
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 28 Years to 55 Years

Eligibility

INCLUSION CRITERIA

The subjects will be included in the study based on the following criteria:

1. Able to understand and give written, voluntary informed consent for the study

2. Healthy adult male volunteers between 28 to 55 years of age (both inclusive)

3. Body Mass Index (BMI) = 18.50 and = 30.00 kg/m2 at the time of screening

4. Medically healthy with no clinically significant medical history, vital signs, physical examination, and laboratory profiles

5. Normal or clinically acceptable 12-lead electrocardiogram, QT interval corrected for heart rate (QTc interval)* = 450 msec at the time of screening

6. Subjects with negative alcohol test (breath analyzer or any suitable test) at the time of screening and admission (pre-dose)

7. Male subjects with female partners who agree to use effective contraception during study#

8. Male subjects who agree not to donate sperm during study

9. Willing and able to comply with the protocol requirements

10. Willing for multiple sampling and admission at the phase 1 study site day before dosing *Note: QTc interval will be calculated using the Bazette and Fridericia formula # Effective contraception: A non-vasectomised Male volunteers with female partners of child bearing potential should use dual method of contraception i.e. condom with spermicide method of contraception. Female partners should use hormonal or non-hormonal method of contraception. (No restrictions are required for a vasectomised male provided his vasectomy has been performed 4 months or more prior to the first dosing. A male who has been vasectomised less than 4 months prior to the first dosing must follow the same restrictions as a non-vasectomised male). EXCLUSION CRITERIA

The subjects will be excluded from the study based on the following criteria:

1. Known hypersensitivity to Denosumab or to any of the components of the study drug

2. Participating or has received any investigational drug (or is currently using an investigational device) within 30 days before receiving the study drug, or at least 10 times the respective elimination halflife (whichever period is longer) *

• For monoclonal antibody refer exclusion criteria number 18 and 19

3. A serious infection (associated with housing and/or required intravenous anti-infectives) within 6 months before study drug administration and/or any active infection within 4 weeks of screening requiring oral or systemic antibiotics

4. History of significant drug abuse within 12 months before screening or a use of soft drugs (such as marijuana) within 3 months before the screening visit or hard drugs (such as cocaine, phencyclidine, and crack etc.) within 12 months before screening

5. Smokers who smoke = 10 cigarettes or equivalent per day within 90 days prior to screening

6. Subjects with positive urine screen for drugs of abuse at the time of screening or check-in

7. Subjects with Urine Cotinine > 500ng/ml at the time of screening or check-in

8. Subjects with risk of osteonecrosis of the jaw i.e. poor oral hygiene, periodontal disease, poorly fitting dentures, history of dental disease or have undergone invasive dental procedures e.g. tooth extractions within last 6 months prior to screening.

9. Subjects with a predictable risk of invasive dental surgery during the 9 months after dosing or with planned invasive dental procedure

10. Subjects with known bone disease or recent fracture or abnormalities of calcium metabolism

11. Loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL within 30 days, or more than 499 mL within 56 days before dosing

12. History of immunodeficiency (including those subjects with a positive test for human immunodeficiency virus [HIV] at screening)

13. Have a positive result for hepatitis B antigen test (HBsAg) or hepatitis C antibody test (HCAb), or show evidence of possible infection

14. Major surgical procedure within 28 days of dose of investigational product.

15. Male subjects having pregnant female partner at the time of screening.

16. Subject with a history of recurrent or chronic infections

17. Received live vaccines within 4 weeks or who may require live vaccine(s) during the study duration

18. Prior use of denosumab

19. Have previously been exposed to a monoclonal antibody or fusion protein within 270 days (other than denosumab) prior to randomisation and/or there is confirmed evidence or clinical suspicion of immunogenicity from previous exposure to a monoclonal antibody or fusion protein.

20. Any reason/condition which would preclude subject's participation in the study as per the Investigator's opinion or warnings and contraindications in the prescribing information of Prolia

21. Subjects with suspected signs and symptoms of COVID-19/confirmed novel coronavirus infection (COVID-19).

Related Conditions & MeSH terms

• Healthy Male Subjects

Intervention

Biological:
• ENZ215
healthy volunteers receive ENZ215 (60mg) once
• EU Sourced Prolia
healthy volunteers receive Denosumab (60mg) once
• US Sourced Prolia
healthy volunteers receive Denosumab (60mg) once

Locations

Country	Name	City	State
Bulgaria	MC Comac Medical	Sofia	Sofia City Province
Poland	MTZ Clinical Research powered by Pratia, Pratia S.A	Warszawa

Sponsors (2)

Lead Sponsor	Collaborator
Enzene Biosciences Ltd.	Alkem Laboratories Ltd

Countries where clinical trial is conducted

Bulgaria,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of subjects who developed denosumab neutralizing antibodies and antidrug antibodies		270 days
Other	Incidence of adverse events		270 days
Primary	Maximum observed drug concentration (Cmax) of ENZ215 and EU- and US-sourced Prolia®		270 days
Primary	Area under the drug concentration-time curve from day 0 to day 270 (AUC0-t) of ENZ215 and EU- and US-sourced Prolia®		270 days
Primary	Area under the drug concentration-time curve from time 0 to infinity (AUC0-inf) of ENZ215 and EU- and US-sourced Prolia®		270 days
Secondary	Partial area under the drug concentration-time curve from time 0 (pre-dose) to day 28		28 days
Secondary	Time to reach Cmax (tmax)		270 days
Secondary	Terminal elimination half-life (t1/2)		270 days
Secondary	Apparent systemic clearance (CL/F)		270 days
Secondary	Area under the effect curve (AUEC) from time 0 to Day 270 for serum CTX-1 percent inhibition		270 days