Romosozumab + Zoledronic Acid for Osteoporosis
(RUBI Trial)
Recruiting in Palo Alto (17 mi)
Age: 65+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Susan L. Greenspan
Must not be taking: Bisphosphonates, Denosumab, Teriparatide, Romosozumab
Disqualifiers: Recent CVD, Renal insufficiency, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of this study is to find out if one year of romosozumab (Evenity®), a monthly injection given in the arm under the skin, prior to an infusion of zoledronic acid Reclast®, works to treat bone loss and prevent it from worsening in older women (ages 65 and older) who have osteoporosis and reside in long-term care (LTC) facilities.
Do I need to stop my current medications for the trial?
You can continue taking medications that affect bone and mineral metabolism, like glucocorticoids and anticonvulsants, and osteoporosis agents like estrogen/progesterone or raloxifene if prescribed by your doctor. However, you cannot participate if you are currently on certain osteoporosis therapies like bisphosphonates, denosumab, teriparatide, abaloparatide, or romosozumab.
What data supports the effectiveness of the drug Romosozumab for osteoporosis?
Research shows that Romosozumab is effective in treating osteoporosis by increasing bone density and reducing the risk of fractures, especially in postmenopausal women. Studies have demonstrated that it works well when used alone or followed by another drug called denosumab, leading to ongoing improvements in bone health.
12345Is Romosozumab safe for humans?
Romosozumab has been studied for safety in several clinical trials for osteoporosis, and while it is generally considered safe, there may be potential cardiovascular risks (related to the heart and blood vessels) associated with its use. The FDA's adverse event reporting system is used to monitor any unexpected side effects.
26789How does the drug romosozumab differ from other osteoporosis treatments?
Romosozumab is unique because it is a monoclonal antibody that both promotes bone formation and reduces bone breakdown by targeting sclerostin, a protein that regulates bone growth. This dual action leads to rapid and significant increases in bone density, which is more effective than many other treatments like bisphosphonates or parathyroid hormone analogs. It is typically followed by another drug to maintain its benefits.
410111213Eligibility Criteria
This trial is for women aged 65 or older with osteoporosis, living in long-term care facilities. They must have a bone density score of -2.5 SD or lower, a history of fractures, or meet certain risk criteria. Excluded are non-walkers, those with recent severe heart issues, kidney problems preventing IV treatment, recent stroke or heart attack victims, current users of specific osteoporosis meds and very low vitamin D levels.Inclusion Criteria
Willing and able to complete the informed consent process or provide consent by proxy
I am a woman aged 65 or older living in a care facility.
I have osteoporosis or had a major bone fracture.
Exclusion Criteria
Your vitamin D levels are lower than 25 ng/mL.
I am currently taking or have recently taken medication for osteoporosis.
I am unable to walk on my own.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive monthly subcutaneous injections of Romosozumab for 12 months, followed by a Zoledronic Acid infusion
12 months
12 visits (in-person) for injections, 1 visit (in-person) for infusion
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 months
Regular monitoring visits
Participant Groups
The study tests if romosozumab injections followed by zoledronic acid infusion can improve bone health in elderly women with osteoporosis at LTC facilities. It compares the effects to placebo treatments alongside standard calcium and vitamin D supplements.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Romosozumab, then Zoledronic AcidExperimental Treatment3 Interventions
Monthly dose: 210 mg Romosozumab subcutaneous injections; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements); all participants will receive 5 mg Zoledronic Acid IV infusion at the Month 12 visit.
Group II: Placebo, then Zoledronic AcidPlacebo Group3 Interventions
Monthly dose: placebo saline subcutaneous injections; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements); all participants will receive 5 mg Zoledronic Acid IV infusion at the Month 12 visit.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UPMC Senior CommunitiesPittsburgh, PA
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Who Is Running the Clinical Trial?
Susan L. GreenspanLead Sponsor
National Institutes of Health (NIH)Collaborator
National Institute on Aging (NIA)Collaborator
References
Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis. [2021]To investigate the effects of prior treatment and determine the predictors of a 12-month treatment response of romosozumab (ROMO) in 148 patients with postmenopausal osteoporosis.
Romosozumab: a Review of Efficacy, Safety, and Cardiovascular Risk. [2021]Authors review the safety and efficacy of romosozumab for the treatment of osteoporosis as demonstrated in three phase III clinical trials and offer insights into the potential cardiovascular risk associated with its use.
Effects of romosozumab or denosumab treatment on the bone mineral density and disease activity for 6 months in patients with rheumatoid arthritis with severe osteoporosis: An open-label, randomized, pilot study. [2022]To investigate effects of romosozumab treatment on disease activity and bone mineral density (BMD) in patients with rheumatoid arthritis (RA) and severe osteoporosis in comparison with effects of denosumab treatment.
[The sequential therapy of romosozumab followed by denosumab for osteoporosis.] [2019]Romosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption by inhibiting sclerostin. In the pivotal Fracture study in postmenopausal women with osteroposis(FRAME)and the extension trial, 12 months of romosozumab led to persistent fracture, especially new vertebral fracture, reduction benefit and ongoing BMD(bone mineral density)gains when follow 24 months of denosumab. The sequence therapy of romosozumab followed by denosumab may be a promising regimen for the treatment of osteoporosis.
Effects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis. [2021]To investigate the effects of prior treatment and the predictors of early treatment response to romosozumab (ROMO) in patients with postmenopausal osteoporosis.
A pharmacovigilance analysis of FDA adverse event reporting system events for romosozumab. [2023]Romosozumab is a novel drug for the treatment of osteoporosis. The adverse reactions of romosozumab still need to be explored. The FDA Adverse Event Reporting System (FAERS) provides an enormous dataset for adverse events (AEs) analysis.
Romosozumab: A Novel Injectable Sclerostin Inhibitor With Anabolic and Antiresorptive Effects for Osteoporosis. [2021]To review the clinical pharmacology, efficacy, and safety of romosozumab, a humanized monoclonal antibody with a novel mechanism of action for monthly injection, and its place in the management of osteoporosis.
Romosozumab versus Teriparatide for the Treatment of Postmenopausal Osteoporosis: A Systematic Review and Meta-analysis through a Grade Analysis of Evidence. [2023]To provide a systematic review about the efficacy and safety of romosozumab and teriparatide for the treatment of postmenopausal osteoporosis.
Romosozumab treatment in postmenopausal women with osteoporosis: a meta-analysis of randomized controlled trials. [2019]To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the safety and efficacy of romosozumab in the treatment of postmenopausal osteoporosis.
Romosozumab: A Review in Postmenopausal Osteoporosis. [2021]Romosozumab (Evenity®), a humanized monoclonal antibody, promotes bone formation and inhibits bone resorption by inhibiting sclerostin, a protein involved in the regulation of bone formation. Subcutaneous romosozumab is approved in several countries, including those of the EU for treating severe osteoporosis as well as in the USA for osteoporosis in postmenopausal women at high risk of fracture. In pivotal phase III trials (FRAME and ARCH), 12 months' once-monthly romosozumab 210 mg significantly reduced vertebral and clinical fracture risk versus placebo and oral alendronate in postmenopausal women with osteoporosis. After patients transitioned from romosozumab to 12-24 months of subcutaneous denosumab or oral alendronate, fracture risks were significantly improved versus placebo-to-denosumab and alendronate-only treatment. In these trials and a phase IIIb trial, romosozumab significantly increased bone mineral density (BMD) relative to placebo, alendronate and subcutaneous teriparatide at 12 months, with these benefits maintained 12-24 months after patients transitioned from romosozumab to alendronate or denosumab in pivotal trials. Romosozumab had a generally manageable tolerability profile. While further clinical experience is needed to more definitively establish its efficacy and safety, including its CV safety, romosozumab extends the treatment options in postmenopausal women with osteoporosis who have a high risk of fracture and in those who have failed or are intolerant to other available osteoporosis therapy.
Effect of Romosozumab Treatment in Postmenopausal Women With Osteoporosis and Knee Osteoarthritis: Results From a Substudy of a Phase 3 Clinical Trial. [2023]Romosozumab is a bone-forming agent approved for osteoporosis treatment. Here we report results of the protocol-specified, noninferiority osteoarthritis substudy of the fracture study in postmenopausal women with osteoporosis (FRAME), which evaluated the effect of romosozumab versus placebo on knee osteoarthritis in patients with a clinical history of osteoarthritis.
Effects of romosozumab with and without active vitamin D analog supplementation for postmenopausal osteoporosis. [2022]Although romosozumab is attracting attentions as one of favorably used drugs in today's osteoporosis treatment, there has been no report discussing the differences in the efficacy of romosozumab in the presence or absence of combined use of active vitamin D analog yet. This prospective cohort investigation compared the effects of 12-month romosozumab treatment to increase bone mineral density (BMD) for postmenopausal osteoporosis to observe the influence of combined vitamin D supplementation.
Clinical Utility of Romosozumab in the Management of Osteoporosis: Focus on Patient Selection and Perspectives. [2022]As one of the most potent osteoanabolic agents with a unique mechanism of action, romosozumab has high efficacy for osteoporosis treatment. It is a monoclonal antibody against sclerostin, a natural inhibitor of the Wnt signaling pathway, and by inhibiting sclerostin, activation of Wnt signaling occurs with a cascade of changes ultimately leading to bone mineral density (BMD) gains. Romosozumab stimulates bone modeling and has a dual effect of activating bone formation while inhibiting bone resorption. With this unique mechanism of action, treatment with romosozumab leads to a rapid and significant gain in BMD; these gains are higher than seen with bisphosphonates, denosumab, or parathyroid hormone (PTH) analogs. The FRAME and ARCH studies represent two pivotal trials demonstrating the efficacy of romosozumab in treating osteoporosis. Treatment with romosozumab should be followed by an antiresorptive agent, as this approach has demonstrated maintenance of or greater increases in BMD and reduced fracture risk even after finishing romosozumab treatment. As an osteoanabolic agent, romosozumab has shown superiority to alendronate in reducing fracture risk, increasing bone density, and potentially more rapid fracture risk reduction. Recent data have suggested that romosozumab prior to antiresorptive therapy may be the ideal treatment sequence, especially in high-risk patients and patients at imminent risk of fracture. Carrying a black box warning, romosozumab should be avoided in patients who have had myocardial infarction or stroke in the past year. Further studies are needed to clarify the increased cardiovascular risk attributed to this drug. Romosozumab has expanded our osteoporosis armamentarium and has enabled novel approaches, including "treat to target." Future studies are needed to evaluate the optimal use sequence and to assess its safety, especially in patients with cardiovascular risk factors.