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

NCT05245669 | Completed Phase 1 Results

• 2 other identifiers: ALK22/ENZ215-DEN12021-004177-32
• Study Type: interventional
• Target: 207
• Locations: 2 countries
• Sites: 2

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.

Conditions

Healthy Male Subjects

Outcome Measures

Primary Outcomes (3)

• Maximum Observed Drug Concentration (Cmax) of ENZ215 and EU- and US-sourced Prolia®

  A total of twenty four blood PK samples of 2.5 mL each were collected from each subject in the study. Pre-dose sample were collected within 30 minutes prior to IP administration. Post-dose samples up to Day 2 were collected within ± 10 minutes, within ± 2 hours from Day 3 to Day 21, within ± 1 day on Day 28, within ± 3 days from Day 42 to Day 180 and within ±5 days from Day 224 to Day 270. Serum concentrations of denosumab were measured at central laboratory by a validated analytical method.

  270 days

• Area Under the Drug Concentration-time Curve From Day 0 to Day 270 (AUC0-t) of ENZ215, EU- and US-sourced Prolia®. and EU- and US-sourced Prolia®

  A total of twenty four blood PK samples of 2.5 mL each were collected from each subject in the study. Pre-dose sample were collected within 30 minutes prior to IP administration. Post-dose samples up to Day 2 were collected within ± 10 minutes, within ± 2 hours from Day 3 to Day 21, within ± 1 day on Day 28, within ± 3 days from Day 42 to Day 180 and within ±5 days from Day 224 to Day 270. Serum concentrations of denosumab were measured at central laboratory by a validated analytical method.

  270 days

• Area Under the Drug Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of ENZ215, EU- and US-sourced Prolia®. and EU- and US-sourced Prolia®

  A total of twenty four blood PK samples of 2.5 mL each were collected from each subject in the study. Pre-dose sample were collected within 30 minutes prior to IP administration. Post-dose samples up to Day 2 were collected within ± 10 minutes, within ± 2 hours from Day 3 to Day 21, within ± 1 day on Day 28, within ± 3 days from Day 42 to Day 180 and within ±5 days from Day 224 to Day 270. Serum concentrations of denosumab were measured at central laboratory by a validated analytical method.

  270 days

Secondary Outcomes (5)

• Partial Area Under the Drug Concentration-time Curve From Time 0 (Pre-dose) to Day 28

  28 days

• Time to Reach Cmax (Tmax)

  270 days

• Terminal Elimination Half-life (t1/2)

  270 days

• Apparent Systemic Clearance (CL/F)

  270 days

• Area Under the Effect Curve (AUEC) From Time 0 to Day 270 for Serum CTX-1 Percent Inhibition Percent Inhibition

  270 days

Other Outcomes (2)

• Number of Subjects Who Developed Denosumab Neutralizing Antibodies and Antidrug Antibodies. Antibodies

  270 days

• Incidence of Adverse Events

  270 days

Study Arms (3)

ENZ215

EXPERIMENTAL

ENZ215 Injection:- 60 mg Denosumab (ENZ215) will be administered subcutaneously on day 1.

Biological: ENZ215

EU Sourced Prolia

ACTIVE COMPARATOR

EU sourced Prolia Injection:- 60 mg Denosumab (EU sourced Prolia) will be administered subcutaneously on day 1.

Biological: EU Sourced Prolia

US Sourced Prolia

ACTIVE COMPARATOR

US sourced Prolia Injection:- 60 mg Denosumab (US sourced Prolia) will be administered subcutaneously on day 1.

Biological: US Sourced Prolia

Interventions

ENZ215 BIOLOGICAL

healthy volunteers receive ENZ215 (60mg) once

ENZ215

EU Sourced Prolia BIOLOGICAL

healthy volunteers receive Denosumab (60mg) once

EU Sourced Prolia

US Sourced Prolia BIOLOGICAL

healthy volunteers receive Denosumab (60mg) once

US Sourced Prolia

Eligibility Criteria

• Age: 28 Years - 55 Years
• Gender Eligibility Details: Healthy adult male of age 28-55 years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subjects will be included in the study based on the following criteria:
• Able to understand and give written, voluntary informed consent for the study
• Healthy adult male volunteers between 28 to 55 years of age (both inclusive)
• Body Mass Index (BMI) ≥ 18.50 and ≤ 30.00 kg/m2 at the time of screening
• Medically healthy with no clinically significant medical history, vital signs, physical examination, and laboratory profiles
• Normal or clinically acceptable 12-lead electrocardiogram, QT interval corrected for heart rate (QTc interval)\* ≤ 450 msec at the time of screening
• Subjects with negative alcohol test (breath analyzer or any suitable test) at the time of screening and admission (pre-dose)
• Male subjects with female partners who agree to use effective contraception during study#
• Male subjects who agree not to donate sperm during study
• Willing and able to comply with the protocol requirements
• 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).

You may not qualify if:

• The subjects will be excluded from the study based on the following criteria:
• Known hypersensitivity to Denosumab or to any of the components of the study drug
• 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) \*
• 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
• 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
• Smokers who smoke ≥ 10 cigarettes or equivalent per day within 90 days prior to screening
• Subjects with positive urine screen for drugs of abuse at the time of screening or check-in
• Subjects with Urine Cotinine \> 500ng/ml at the time of screening or check-in
• 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.
• Subjects with a predictable risk of invasive dental surgery during the 9 months after dosing or with planned invasive dental procedure
• Subjects with known bone disease or recent fracture or abnormalities of calcium metabolism
• 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
• History of immunodeficiency (including those subjects with a positive test for human immunodeficiency virus \[HIV\] at screening)
• Have a positive result for hepatitis B antigen test (HBsAg) or hepatitis C antibody test (HCAb), or show evidence of possible infection
• Major surgical procedure within 28 days of dose of investigational product.

Sponsors & Collaborators

• Enzene Biosciences Ltd.: lead
• Alkem Laboratories Ltd: collaborator

Study Sites (2)

MC Comac Medical

Sofia, Sofia City Province, 1000, Bulgaria

Location

MTZ Clinical Research powered by Pratia, Pratia S.A

Warsaw, 02-172, Poland

Location

Results Point of Contact

• Title: Dr. Akhilesh Sharma
• Organization: Alkem Laboratories Limited

akhilesh.sharma@alkem.com

+91- 9701346369

Study Officials

• Dr. Nadine Abdullah

  Celerion GB Ltd.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Arm 1: ENZ215 Arm 2 : EU Sourced Prolia Arm 3: US Sourced Prolia

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: February 18, 2022
• Study Start: January 10, 2022
• Primary Completion: May 22, 2024
• Study Completion: May 22, 2024
• Last Updated: December 23, 2025
• Results First Posted: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1); PL (1)