Clinical trial NCT05245669: Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity of Biosimilar Denosumab With Prolia® in Healthy Adult Male Volunteers
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Healthy Male Subjects
Lead sponsor: Enzene Biosciences Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Alkem Laboratories Ltd
First posted: 2022-02-18
Enrollment: 207
Sex: MALE
Minimum age (years): 28
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1: ENZ215 Arm 2 : EU Sourced Prolia Arm 3: US Sourced Prolia
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Maximum observed drug concentration (Cmax) of ENZ215 and EU- and US-sourced Prolia®
timeFrame: 270 days
measure: Area under the drug concentration-time curve from day 0 to day 270 (AUC0-t) of ENZ215 and EU- and US-sourced Prolia®
timeFrame: 270 days
measure: Area under the drug concentration-time curve from time 0 to infinity (AUC0-inf) of ENZ215 and EU- and US-sourced Prolia®
timeFrame: 270 days
Secondary outcomes:
measure: Partial area under the drug concentration-time curve from time 0 (pre-dose) to day 28
timeFrame: 28 days
measure: Time to reach Cmax (tmax)
timeFrame: 270 days
measure: Terminal elimination half-life (t1/2)
timeFrame: 270 days
measure: Apparent systemic clearance (CL/F)
timeFrame: 270 days
measure: Area under the effect curve (AUEC) from time 0 to Day 270 for serum CTX-1 percent inhibition
timeFrame: 270 days
Other outcomes:
measure: Number of subjects who developed denosumab neutralizing antibodies and antidrug antibodies
timeFrame: 270 days
measure: Incidence of adverse events
timeFrame: 270 days
Locations:
city: Sofia
country: Bulgaria
facility: MC Comac Medical
state: Sofia City Province
city: Warszawa
country: Poland
facility: MTZ Clinical Research powered by Pratia, Pratia S.A
Study officials:
affiliation: Celerion GB Ltd.
name: Dr. Nadine Abdullah
role: PRINCIPAL_INVESTIGATOR
References: