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About
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.
Full description
Approximately 207 subjects will be enrolled into 3 groups (69 in each group) in parallel. The subjects may be enrolled in multiple groups at the site. All eligible subjects will be assigned to one of the three treatment groups in 1:1:1 ratio i.e. ENZ215 or US-sourced Prolia® or EU-sourced Prolia® to enter into the study period of 39 weeks. The study duration will be approximately 16 months (i.e. 6 months of recruitment period, 4 weeks of screening period and approximately 39 weeks (270 days) of study period).
Each subject will be required to visit the site for a total of 20 visits: visit 1 - screening visit, visit 2 - day 0 to day 2, visit 3 - day 3, visit 4 - day 4, visit 5 - day 5, visit 6 - day 6, visit 7 - day 8, visit 8 - day 10, visit 9 - day 12, visit 10 - day 16, visit 11 - day 21, visit 12 - day 28 (week 4), visit 13 - day 42 (week 6), visit 14 - day 63 (week 9), visit 15 - day 90 (week 13), visit 16 - day 119 (week 17), visit 17 - day 147 (week 21), visit 18 - day 180 (week 26), visit 19 day - 224 (week 32), and visit 20 - day 270 (week 39). A window period of ±1 day is allowed for visit 12 (day 28), window period of ±3 days are allowed from day 42 (week 6) to day 180 (week 26), A window period of ±5 days are allowed from day 224 (week 32) to day 270 (week 39).
End of Study Assessment will be performed on day 270 (week 39) or at the time of early discontinuation of the subject.
Enrollment
Sex
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Volunteers
Inclusion and exclusion criteria
INCLUSION CRITERIA
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.
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:
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) *
* For monoclonal antibody refer exclusion criteria number 18 and 19
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.
Male subjects having pregnant female partner at the time of screening.
Subject with a history of recurrent or chronic infections
Received live vaccines within 4 weeks or who may require live vaccine(s) during the study duration
Prior use of denosumab
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.
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
Subjects with suspected signs and symptoms of COVID-19/confirmed novel coronavirus infection (COVID-19).
Primary purpose
Allocation
Interventional model
Masking
207 participants in 3 patient groups
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Central trial contact
Dr. Harish Shandilya
Data sourced from clinicaltrials.gov
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