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

Healthy Volunteers Clinical Trial

— DENARIUS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05323708
• Other study ID #: B1000-NHV-01-G-01
• Status: Completed
• Phase: Phase 1
• Start date: March 9, 2022
• Est. completion date: October 6, 2023

Study information

• Verified date: April 2024
• Source: Biocon Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 190
• Est. completion date: October 6, 2023
• Est. primary completion date: October 6, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 28 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Biological:
• Bmab 1000
60mg/ml Prefilled syringe single dose
• Prolia®
60mg/ml Prefilled syringe single dose

Locations

Country	Name	City	State
United States	Biotrial Inc	Newark	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Biocon Biologics UK Ltd	Biotrial

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUCinf (Area Under the Concentration infinity)	Area under the concentration-time curve from time zero to infinity	0 to 36 week
Primary	AUClast (Area Under the Concentration last)	Area under the concentration-time curve from time zero to last quantifiable concentration	0 to 36 week
Primary	Cmax	Maximum serum concentration	0 to 36 week
Secondary	Tmax	Time to reach Cmax	0 to 36 week
Secondary	t1/2	Terminal half-life	0 to 36 week
Secondary	Kel	Terminal elimination rate constant (kel)	0 to 36 week
Secondary	Vd/F	Apparent volume of distribution	0 to 36 week
Secondary	Cl/F	Apparent clearance	0 to 36 week
Secondary	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
Secondary	Emax of sCTX	Maximal inhibitory effect (Emax) of sCTX	0 to 36 week
Secondary	Incidence of TEAEs(Treatment Emergent Adverse Events)	Experience at least 1 TEAE	0 to 36 week
Secondary	Incidence of SAEs(Serious Adverse Events)	Experience at least 1 SAE	0 to 36 week
Secondary	Incidence of ADAs (Anti-Drug Antibodies)	Incidence of ADAs to denosumab	0 to 36 week
Secondary	Titer of ADAs	Titer of ADAs to denosumab	0 to 36 week