Clinical trial NCT05323708: Comparison of Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Bmab 1000 and Prolia® in Normal Healthy Volunteers: DENARIUS: DENosumab Pharmacokinetic equivAlence tRIal in Healthy volUnteerS
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Biocon Limited
Sponsor class: INDUSTRY
Collaborators: name: Biotrial
First posted: 2022-04-12
Enrollment: 190
Sex: ALL
Minimum age (years): 28
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: AUCinf (Area Under the Concentration infinity)
timeFrame: 0 to 36 week
measure: AUClast (Area Under the Concentration last)
timeFrame: 0 to 36 week
measure: Cmax
timeFrame: 0 to 36 week
Secondary outcomes:
measure: Tmax
timeFrame: 0 to 36 week
measure: t1/2
timeFrame: 0 to 36 week
measure: Kel
timeFrame: 0 to 36 week
measure: Vd/F
timeFrame: 0 to 36 week
measure: Cl/F
timeFrame: 0 to 36 week
measure: AUEC of sCTX
timeFrame: 0 to 36 week
measure: Emax of sCTX
timeFrame: 0 to 36 week
measure: Incidence of TEAEs(Treatment Emergent Adverse Events)
timeFrame: 0 to 36 week
measure: Incidence of SAEs(Serious Adverse Events)
timeFrame: 0 to 36 week
measure: Incidence of ADAs (Anti-Drug Antibodies)
timeFrame: 0 to 36 week
measure: Titer of ADAs
timeFrame: 0 to 36 week
Other outcomes:
Locations:
city: Newark
country: United States
facility: Biotrial Inc
state: New Jersey
Study officials:
References: