What is the mechanism of action of this treatment?

RANKL inhibitors, such as denosumab (Prolia®), work by targeting and inhibiting the RANK ligand, a key regulator of osteoclast activity. This inhibition prevents the formation, function, and survival of osteoclasts, which are cells responsible for bone resorption. For healthy subjects, this mechanism is crucial as it helps maintain bone density and strength, reducing the risk of fractures and other skeletal-related events. By modulating bone remodeling processes, RANKL inhibitors can effectively prevent bone loss and promote overall skeletal health.

What side effects are associated with this type of intervention?

Common side effects of RANKL inhibitors like denosumab (Prolia®) include back pain, pain in extremities, musculoskeletal pain, hypercholesterolemia, and cystitis. Serious side effects can include hypocalcemia, serious infections, dermatologic reactions, and osteonecrosis of the jaw. It is important for patients to discuss these potential side effects with their healthcare provider to weigh the benefits and risks of treatment.

What prior FDA approvals exist?

Denosumab, marketed as Prolia®, is a RANKL inhibitor that has been approved by the FDA for the treatment of osteoporosis in postmenopausal women and men at high risk of fractures, as well as for the prevention of skeletal-related events in patients with bone metastases from solid tumors. The trial Bmab 1000 is studying a similar mechanism of action in healthy volunteers to compare its pharmacokinetics, pharmacodynamics, safety, and tolerability with Prolia®.

What other types of research exist?

Promising novel alternatives to Bmab 1000 (RANKL inhibition) for healthy subjects in 2024 include denosumab, which has shown long-term efficacy in reducing fracture risk, and newer antiresorptive agents like abaloparatide and romosozumab. These alternatives have demonstrated significant benefits in bone density and fracture prevention in recent clinical trials.

← Back to Search

Monoclonal Antibodies

Bmab 1000 vs Prolia® in Healthy Subjects (DENARIUS Trial)

Phase 1

Waitlist Available

Research Sponsored by Biocon Biologics UK Ltd

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Gender: Male

Age: 28-55 years, inclusive at screening.

Must not have

Known history of previous exposure to denosumab.

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.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 0 to 36 week

Awards & highlights

No Placebo-Only Group

All Individual Drugs Already Approved

Summary

This trial is testing two medications, Bmab 1000 and Prolia®, given as injections under the skin. It involves healthy volunteers to see how these drugs are absorbed and processed by the body, their effects, and their safety. The study lasts several months.

Who is the study for?

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.

What is being tested?

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).

What are the potential side effects?

While specific side effects are not listed here as it's a study on healthy volunteers, typical side effects from such medications may include skin reactions at injection sites, low calcium levels in blood, infections like sinusitis or urinary tract infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

You must be male.

Select...

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

You have taken denosumab before.

Select...

You have taken certain medications for bone health like bisphosphonates or teriparatide.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 0 to 36 week

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~0 to 36 week

This trial's timeline: 3 weeks for screening, Varies for treatment, and 0 to 36 week for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

AUCinf (Area Under the Concentration infinity)

AUClast (Area Under the Concentration last)

Cmax

Secondary study objectives

AUEC of sCTX

Cl/F

Emax of sCTX

+8 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Bmab 1000, A single 60 mg dose of Bmab 1000 administered by subcutaneous injection.Experimental Treatment1 Intervention

Group II: Prolia®, A single 60 mg dose of Prolia® administered by subcutaneous injection.Active Control1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bmab 1000

2022

Completed Phase 3

~670

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

RANKL inhibitors, such as denosumab (Prolia®), work by targeting and inhibiting the RANK ligand, a key regulator of osteoclast activity. This inhibition prevents the formation, function, and survival of osteoclasts, which are cells responsible for bone resorption. For healthy subjects, this mechanism is crucial as it helps maintain bone density and strength, reducing the risk of fractures and other skeletal-related events. By modulating bone remodeling processes, RANKL inhibitors can effectively prevent bone loss and promote overall skeletal health.

[Evaluation of the treatment and efficacy of osteoporosis].[A meeting Report on the 2018 annual meeting of ASBMR-Clinical practice of the osteoporosis-.][ASBMR Topics from clinical research concerning bone and mineral metabolism other than osteoporosis.]