Bmab 1000 vs Prolia® in Healthy Subjects

(DENARIUS Trial)

Overseen By Sivakumar Vaidyanathan, M Pharm

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Biocon Biologics UK Ltd

Must not be taking: Bisphosphonates, Strontium, Fluoride, others

Disqualifiers: Bone disease, Renal disease, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare how two treatments, Bmab 1000 and Prolia®, behave in the body and assess their safety and tolerability. Researchers are testing these treatments in healthy individuals, meaning participants do not have underlying health conditions that could affect the results. Each participant will receive a single injection of either Bmab 1000 or Prolia®. Ideal candidates for this trial are healthy individuals without significant medical issues or conditions affecting bone health. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who have used certain bone-modifying medications. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Bmab 1000 is generally safe and well-tolerated. In earlier studies, about 59.2% of patients experienced side effects after starting treatment with Bmab 1000, slightly less than the 63.3% reported for Prolia®. Both treatments had similar types of side effects.

Further research indicates that Bmab 1000's safety profile closely resembles that of Prolia®, suggesting it is equally well-tolerated. These findings, based on trials with postmenopausal women, provide useful safety information.

Prolia® has already received approval for other conditions, which adds confidence in its safety. Overall, existing research suggests that both treatments have a similar safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Bmab 1000 because it offers a fresh approach to bone health management. Unlike standard treatments like bisphosphonates or Prolia®, which mainly work by slowing bone loss, Bmab 1000 may have a unique mechanism that could enhance bone formation. This single-dose treatment is administered via a simple subcutaneous injection, which is convenient for patients. These features could potentially lead to better outcomes for maintaining bone density and strength.

What evidence suggests that this trial's treatments could be effective?

This trial will compare Bmab 1000 with Prolia® in healthy subjects. Research has shown that Bmab 1000, one of the treatments in this trial, works as well as Prolia® in increasing bone strength in the lower back, which is important for treating osteoporosis. Studies have found that Bmab 1000 can significantly improve bone strength from the starting point. Prolia®, the other treatment option in this trial, is already approved and strengthens bones while reducing fracture risk in people with osteoporosis. Bmab 1000 aims to achieve similar results, offering another option with comparable effectiveness. Both treatments are administered through an injection under the skin, providing convenience for patients. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

Healthy men and women aged 28-55, weighing 60-95 kg (55-95 kg for Japanese subjects), with a BMI of 18.0 to 30.0 can join this trial. Participants must have normal ECGs and vital signs, not be allergic to monoclonal antibodies or denosumab components, and should not have any significant health issues or history of bone disease.

Inclusion Criteria

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.

You are between 28 and 55 years old when you are screened.

You weigh between 60 and 95 kilograms during screening.

Exclusion Criteria

Unable to follow protocol instructions or not likely to complete the study in the opinion of the Investigator or their designee.

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.

You have a history of allergies to certain medications, food, latex, or have a condition called fructose intolerance.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive a single 60 mg dose of either Bmab 1000 or Prolia® administered subcutaneously

1 day

1 visit (in-person)

Follow-up

Participants are monitored for pharmacokinetics, pharmacodynamics, safety, and tolerability up to 36 weeks post randomization

36 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bmab 1000
• Prolia®

Trial Overview

The DENARIUS study is testing the effects, safety, and tolerability of two drugs: Bmab 1000 and Prolia® in healthy volunteers. It aims to see if these drugs behave similarly in the body by comparing their pharmacokinetics (how they're processed) and pharmacodynamics (their effects).

How Is the Trial Designed?

Group I: Bmab 1000, A single 60 mg dose of Bmab 1000 administered by subcutaneous injection. Experimental Treatment 1 Intervention

Group II: Prolia®, A single 60 mg dose of Prolia® administered by subcutaneous injection. Active Control 1 Intervention

Who Is Running the Clinical Trial?

Biocon Biologics UK Ltd

Lead Sponsor

Trials

5

Recruited

1,600+

Biotrial

Industry Sponsor

Trials

15

Recruited

1,100+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05345691

Study Details | NCT05345691 | Comparison of Efficacy, ...

Percentage Change in Lumbar Spine BMD, To demonstrate equivalent efficacy between Bmab 1000 and Prolia® based on percentage change from baseline at Week 26 in ...

2.

ema.europa.eu

ema.europa.eu/en/documents/rmp/vevzuo-epar-risk-management-plan_en.pdf

Vevzuo, INN-denosumab - European Medicines Agency

Safety, and Tolerability of Bmab 1000 and Prolia® in Normal Healthy Volunteers. • Study B1000-PMO-03-G-02: A Randomized, Double-Blind, Multicenter, Parallel ...

3.

clinicaltrialsregister.eu

clinicaltrialsregister.eu/ctr-search/trial/2021-006545-36/EE

Clinical Trials Register

a. To demonstrate equivalent efficacy between Bmab 1000 and Prolia based on percentage change from baseline at Week 52 in lumbar spine BMD (Co- ...

4.

ctv.veeva.com

ctv.veeva.com/study/comparison-of-efficacy-pharmacodynamics-safety-and-immunogenicity-between-bmab-1000-and-prolia-r-i

Comparison of Efficacy, Pharmacodynamics, Safety, and ...

Comparison of Efficacy, Pharmacodynamics, Safety, and Immunogenicity Between Bmab 1000 and Prolia® in Postmenopausal Women With Osteoporosis (DEVOTE). B. Biocon.

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05323708

Study Details | NCT05323708 | Comparison of ...

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

6.

ema.europa.eu

ema.europa.eu/en/documents/assessment-report/vevzuo-epar-public-assessment-report_en.pdf

Vevzuo, INN-denosumab - European Medicines Agency

Study B1000-PMO-03-G-02: a confirmatory Phase 3 study comparing the efficacy, pharmacodynamics. (PD), safety, immunogenicity, and PK of Bmab ...

7.

acrabstracts.org

acrabstracts.org/abstract/a-randomized-double-blind-multicenter-parallel-arm-phase-3-study-to-compare-the-efficacy-pharmacodynamics-safety-and-immunogenicity-between-bmab-1000-and-prolia-in-postmenopausal-women-with-oste/

A Randomized, Double-blind, Multicenter, Parallel-arm ...

Bmab-1000 was safe and well tolerated compared with Prolia. The proportion of patients reporting treatment-emergent adverse events (TEAEs; 59.2%, Bmab1000; 63.3 ...