Comparison of Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Bmab 1000 and Prolia® in Normal Healthy Volunteers: DENARIUS: DENosumab Pharmacokinetic equivAlence tRIal in Healthy volUnteerS (DENARIUS)

A Randomized, Double-blind, Two-arm, Single-dose, Parallel-Group Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Bmab 1000 and Prolia® in Normal Healthy Volunteers

This study is to compare the Pharmacokinetics, Pharmacodynamics, safety, and tolerability of Bmab 1000 and Prolia® in normal healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: Bmab 1000; Biological: Prolia®

Detailed Description

This study will consist of 2 study periods: Screening period (4 weeks) and Treatment period (Dosing and follow-up).

In this double-blind, 2-arm study, the eligible subjects will be randomized in a 1:1 ratio to receive either Bmab 1000 or Prolia® on Day 1. The interventions (Bmab 1000 or Prolia®) will be administered subcutaneously. End-of-study visit will be at Week 36 post randomization.

The total duration of study participation for a subject will be up to 40 weeks.

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Biotrial Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Gender: Male or Female
2. Age: Male subjects: 28-55 years, inclusive at screening; Female subjects: 28-45 years, inclusive at screening.
3. Weight: For non-Japanese subjects 60.0-95.0 kg, inclusive at screening. For Japanese subjects 55.0-95.0 kg, inclusive at screening.
4. Body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive, at screening.
5. Vital signs showing no clinically relevant deviations according to the Investigator's judgment or their designee's. In the case of subjects > 45 year-old, if a value of SBP above 145 mmHg is confirmed on rechecking the BP after a period of rest, this subject will not be included in the study.
6. 12-lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the Investigator or their designee.

Exclusion Criteria:

1. Evidence of clinically relevant pathology: Like have a history of and/or current clinically significant gastrointestinal, renal, hepatic, cardiovascular, haematological, pulmonary, neurologic, metabolic, psychiatric disorder, drug or alcohol abuse, or allergic disease excluding mild asymptomatic seasonal allergies. Have a history of malignancy (including lymphoma, leukaemia, and skin cancer).
2. Unable to follow protocol instructions or not likely to complete the study in the opinion of the Investigator or their designee.
3. History of relevant drug and/or food allergies (including hypersensitivity to any recombinant protein drug or any of the constituents of denosumab, or latex allergy or hereditary problems of fructose intolerance).
4. Known history of previous exposure to denosumab.
5. Have previously been exposed to a monoclonal antibody or fusion protein (other than denosumab) within 270 days (or 5 half-lives whichever is the longest) prior to randomization and/or there is confirmed evidence or clinical suspicion of immunogenicity from previous exposure to a monoclonal antibody or fusion protein.
6. Prior diagnosis of bone disease, or any condition that will affect bone metabolism such as, but not limited to: osteoporosis, osteogenesis imperfect, hyperparathyroidism, hyperthyroidism, hypothyroidism, osteomalacia, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, current flare-up of osteoarthritis and/or gout, active malignancy, renal disease (defined as glomerular filtration rate < 60 mL/min), Paget's disease of the bone, recent bone fracture (within 6 months), malabsorption syndrome.
7. Any use of the following bone modifying medications, with no limitation on time since administration: e.g.intravenous bisphosphonates, strontium, fluoride (if administered in treatment of osteoporosis),romosozumab, teriparatide or any parathyroid hormone analogs, calcitonin, and cinacalcet.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bmab 1000, A single 60 mg dose of Bmab 1000 administered by subcutaneous injection.	Biological: Bmab 1000; 60mg/ml Prefilled syringe single dose
Active Comparator: Prolia®, A single 60 mg dose of Prolia® administered by subcutaneous injection.	Biological: Prolia®; 60mg/ml Prefilled syringe single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCinf (Area Under the Concentration infinity)	Area under the concentration-time curve from time zero to infinity	0 to 36 week
AUClast (Area Under the Concentration last)	Area under the concentration-time curve from time zero to last quantifiable concentration	0 to 36 week
Cmax	Maximum serum concentration	0 to 36 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	Time to reach Cmax	0 to 36 week
t1/2	Terminal half-life	0 to 36 week
Kel	Terminal elimination rate constant (kel)	0 to 36 week
Vd/F	Apparent volume of distribution	0 to 36 week
Cl/F	Apparent clearance	0 to 36 week
AUEC of sCTX	Area under the effect curve (AUEC) of serum concentration of C-terminal telopeptide of Type 1 collagen (sCTX)	0 to 36 week
Emax of sCTX	Maximal inhibitory effect (Emax) of sCTX	0 to 36 week
Incidence of TEAEs(Treatment Emergent Adverse Events)	Experience at least 1 TEAE	0 to 36 week
Incidence of SAEs(Serious Adverse Events)	Experience at least 1 SAE	0 to 36 week
Incidence of ADAs (Anti-Drug Antibodies)	Incidence of ADAs to denosumab	0 to 36 week
Titer of ADAs	Titer of ADAs to denosumab	0 to 36 week

Collaborators and Investigators

• Sponsor: Biocon Biologics UK Ltd
• Collaborators: Biotrial

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2022
• Primary Completion (Actual): October 6, 2023
• Study Completion (Actual): October 6, 2023

Study Registration Dates

• First Submitted: March 15, 2022
• First Submitted That Met QC Criteria: April 11, 2022
• First Posted (Actual): April 12, 2022

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: B1000-NHV-01-G-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No