Denosumab Switch for Osteoporosis

JF
JM
Overseen ByJosh Melnick, MPH
Age: 18+
Sex: Any
Trial Phase: Phase 4
Sponsor: University of Alabama at Birmingham
Must be taking: Glucocorticoids
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 4 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to transition osteoporosis patients from denosumab, a bone-strengthening medication, to other treatments to determine which option best controls bone turnover. It compares starting zoledronic acid at two different times or switching to alendronate, both alternatives for ongoing bone health. Patients who have used prednisone or similar medications for over three months and have low bone density or a history of fractures might be suitable candidates. The goal is to find the most effective way to manage bone health after stopping denosumab. As a Phase 4 trial, this research involves FDA-approved treatments and aims to enhance understanding of their benefits for more patients.

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 does require that you have been on glucocorticoids for at least 3 months and continue them for at least 6 more months. If you are taking bisphosphonates, you must not have used them in the past 2 years.

What is the safety track record for these treatments?

Studies have shown that both denosumab and zoledronic acid are safe and effective for treating osteoporosis. A large study found their safety to be similar, indicating comparable risks of side effects. This finding reassures those switching from denosumab to zoledronic acid.

Research indicates that when switching from denosumab to alendronate, alendronate effectively maintains the bone strength gained with denosumab. This suggests that the switch is generally well-tolerated.

Overall, these treatments are considered safe for managing osteoporosis, with evidence supporting their safety and effectiveness.12345

Why are researchers enthusiastic about this study treatment?

Denosumab is unique because it is a monoclonal antibody that targets RANK ligand, a protein involved in the formation, function, and survival of osteoclasts, which are cells that break down bone. This mechanism is different from most standard treatments for osteoporosis, like bisphosphonates, which work by inhibiting osteoclast-mediated bone resorption. Researchers are excited about the potential of switching from Denosumab to other therapies like zoledronic acid or alendronate because it might offer a more tailored approach to maintaining bone density after initial treatment, possibly reducing the risk of rapid bone loss once Denosumab is stopped. This approach could provide more personalized and effective long-term management of osteoporosis by addressing the specific needs of patients transitioning off Denosumab.

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

This trial will compare different treatment strategies for osteoporosis following initial treatment with denosumab. Research has shown that denosumab reduces fracture risk more effectively than zoledronic acid in people with osteoporosis. Specifically, studies indicate that denosumab lowers fracture risk by 26% to 34% more than zoledronic acid in various scenarios. However, switching from denosumab to zoledronic acid, as tested in this trial, can make maintaining bone density challenging, with some patients experiencing about a 5.5% drop in bone mineral density (BMD). Additionally, denosumab proves more effective than alendronate, reducing fracture risk by 36% to 50% across different measures. While both zoledronic acid and alendronate are effective treatments for osteoporosis, denosumab often provides superior fracture prevention.16789

Are You a Good Fit for This Trial?

This trial is for men and women aged 18 or older who have been using glucocorticoids at a certain dose for over 3 months and will continue for at least another six. They must have osteoporosis as shown by bone density scores, or a history of fractures with less severe bone loss. Exclusions include various other bone diseases, recent cancer, dental issues, malnutrition disorders, pregnancy/breastfeeding without contraception use, and intolerance to study drugs.

Inclusion Criteria

I have been taking a steroid medication equivalent to more than 7.5 mg of prednisone daily for over 3 months and will continue for at least 6 months.
My bone density is low, or I've had a fracture due to weak bones.

Exclusion Criteria

I have been diagnosed with Addison's disease.
Not a good candidate for study participation in opinion of investigator
I cannot take denosumab due to bad reactions or allergies.
See 27 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks
1 visit (in-person)

Treatment

Participants switch from Denosumab to either early or late Zoledronic Acid or Alendronate

6-9 months
Regular visits for treatment administration

Follow-up

Participants are monitored for changes in bone turnover markers and safety

6 months
2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

  • Denosumab
Trial Overview The study tests if switching from Denosumab (DMAB) to 'late' zoledronic acid (9 months after last DMAB dose) versus 'early' zoledronic acid (6 months after last DMAB dose) or weekly alendronate affects bone turnover markers in patients on long-term steroids differently.
How Is the Trial Designed?
3Treatment groups
Active Control
Group I: DMAB to "Early" Zoledronic Acid (ZA)Active Control1 Intervention
Group II: Denosumab (DMAB) to Alendronate (ALN)Active Control1 Intervention
Group III: DMAB to "Late" ZAActive Control1 Intervention

Denosumab is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺
Approved in European Union as Prolia for:
🇺🇸
Approved in United States as Prolia for:
🇨🇦
Approved in Canada as Prolia for:
🇯🇵
Approved in Japan as Prolia for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials
1,677
Recruited
2,458,000+

Vrije Universiteit Brussel

Collaborator

Trials
213
Recruited
272,000+

Maastricht University

Collaborator

Trials
246
Recruited
13,190,000+

Amgen

Industry Sponsor

Trials
1,508
Recruited
1,433,000+
Founded
1980
Headquarters
Thousand Oaks, USA
Known For
Human Therapeutics
Top Products
Enbrel, Prolia, Neulasta, Otezla
Robert A. Bradway profile image

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton profile image

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

Denosumab (XGEVA®) is a monoclonal antibody that effectively inhibits bone resorption by preventing the activation of osteoclasts, making it a targeted treatment for patients with bone metastases.
In Phase 3 clinical studies, denosumab was found to be superior to zoledronic acid in delaying skeletal-related events (SREs) by a median of 8.2 months, suggesting it may be a more effective treatment option for these patients.
Quantitative pharmacology of denosumab in patients with bone metastases from solid tumors.Perez Ruixo, JJ., Doshi, S., Sohn, W., et al.[2015]
Denosumab, a monoclonal antibody that targets RANKL, significantly reduces the risk of fractures in postmenopausal women with osteoporosis, showing a 68% reduction in new vertebral fractures and a 40% reduction in hip fractures over a 3-year trial.
Long-term treatment with denosumab did not show increasing trends in adverse events, indicating that its safety profile remains stable over 6 years, even when comparing data from initial placebo recipients who later received the treatment.
Safety Observations With 3 Years of Denosumab Exposure: Comparison Between Subjects Who Received Denosumab During the Randomized FREEDOM Trial and Subjects Who Crossed Over to Denosumab During the FREEDOM Extension.Watts, NB., Brown, JP., Papapoulos, S., et al.[2018]
Denosumab, a monoclonal antibody that inhibits RANKL, shows consistent pharmacokinetics across a large population of 1,076 subjects, including both healthy individuals and cancer patients, indicating its effectiveness in preventing osteoclast activation and survival.
The study found that after administering denosumab, over 95% of patients achieved more than 97% RANKL occupancy, suggesting that dosage adjustments based on body weight, age, race, or tumor type are unnecessary for patients with bone metastases.
Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours.Gibiansky, L., Sutjandra, L., Doshi, S., et al.[2021]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/38753892/
Comparative effectiveness of denosumab vs alendronate ...Denosumab reduced the risk of MOP fractures by 9% at year 1, 12% at year 2, 18% at year 3, and 31% at year 5. An increase in the magnitude of ...
Comparative effectiveness of denosumab vs alendronate ...Overall, denosumab reduced the risk of MOP by 39%, hip by 36%, NV by 43%, NHNV by 50%, and HV fractures by 30% compared with alendronate.
Results for Postmenopausal OsteoporosisIn a 1-year study, women who switched from alendronate to Prolia® showed a significant increase in bone mineral density (BMD) at the hip and the lumbar spine ...
Comparison Between Alendronate and Denosumab in ...Treatment with denosumab was associated with a 66% risk reduction in major fractures compared with alendronate (odds ratio, 0.34; P < .01).
Efficacy Data | RWE: Prolia® vs. alendronateProlia demonstrated superior fracture risk reduction vs alendronate, with a 36% to 50% greater reduction across multiple endpoints.
Bone Mineral Density After Transitioning From Denosumab to ...Alendronate can effectively maintain the BMD gains accrued after 1 year of denosumab in most patients, regardless of baseline characteristics.
Efficacy Data: Prolia® vs. alendronate | Official HCP WebsiteProlia demonstrated noninferiority and superiority (vs alendronate) in total hip BMD 1. BMD data results are not meant to imply fracture efficacy.
NEW DATA FROM AMGEN'S PROLIA® (DENOSUMAB ...Prolia (denosumab) injection reduced fracture risk in patients versus oral alendronate, a frequently prescribed bisphosphonate treatment.
Clinical Guidance on the Sequential and Combined Use of ...The purpose of this guidance is provide-evidence based criteria-for-use for the selection of pharmacotherapy to prevent and treat osteoporosis.
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Terms of Service·Privacy Policy·Cookies·Security