Romosozumab + Denosumab for Osteoporosis
Recruiting in Palo Alto (17 mi)
Overseen byElizabeth Shane, MD
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Columbia University
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The overarching goal of the research program is to define optimal treatment for premenopausal women with clinically significant fracture syndromes that require medical therapy. The investigators hypothesize that romosozumab will be associated with improvements in bone mass and microarchitecture in premenopausal women, and also that the responses and response rates will exceed those observed in premenopausal women treated with teriparatide. The investigators will test this hypothesis in this phase 2 study of 30 premenopausal women with idiopathic osteoporosis (IOP) who will receive 12M of romosozumab 210 mg monthly followed by 12M of denosumab 60 mg SC q6M. Aim 1 will define the within-group effects of this regimen. Aim 2 will compare results from participants treated with romosozumab-denosumab to the investigator's well-characterized historical controls treated with teriparatide followed by denosumab.
Do I need to stop my current medications to join the trial?
The trial requires stopping certain medications before joining. If you're on drugs for osteoporosis like raloxifene, bisphosphonates, or denosumab, you must stop them for a specific period before participating. For example, you need to wait 3 months after stopping raloxifene or calcitonin, 12 months after stopping certain bisphosphonates, and 18 months after the last dose of denosumab. Other medications like glucocorticoids, anticonvulsants, and anticoagulants also have specific requirements. Check with the trial team for details on your specific medications.
What data supports the idea that Romosozumab + Denosumab for Osteoporosis is an effective drug?
The available research shows that using Romosozumab followed by Denosumab significantly improves bone health in people with osteoporosis. In a study called FRAME, postmenopausal women who took Romosozumab for a year had a 13% increase in spine bone density and a 7% increase in hip bone density. They also had fewer fractures compared to those who took a placebo. After switching to Denosumab, these benefits continued, with a significant reduction in fractures over two years. This combination treatment showed similar bone density improvements in two years as seven years of continuous Denosumab alone.
12345What safety data is available for Romosozumab and Denosumab in treating osteoporosis?
Romosozumab has been evaluated in several studies, including three phase III clinical trials, which demonstrated its efficacy in increasing bone mineral density and reducing fractures. However, there are safety concerns, particularly regarding cardiovascular risks, as major adverse cardiac events were observed in one clinical trial. Other reported adverse effects include arthralgia, headache, and injection site reactions. Romosozumab is recommended for postmenopausal women at high risk for fractures but should be avoided in those with a history of or at high risk for cardiovascular disease. The FDA Adverse Event Reporting System (FAERS) provides additional data on adverse events associated with Romosozumab. Denosumab, marketed as Prolia and Xgeva, is another treatment for osteoporosis, but specific safety data for its combination with Romosozumab is not detailed in the provided research.
678910Eligibility Criteria
This trial is for premenopausal women aged 18-48 with idiopathic osteoporosis, regular menstrual cycles, and no secondary cause of bone loss. Participants must have had low-trauma fractures and a T-score or Z-score β€ -1.5 at certain bone sites. They should agree to highly effective contraception during the study.Inclusion Criteria
I agree to use highly effective birth control during the study.
I am a woman aged 18-48, premenopausal, with regular periods and no osteoporosis.
I have had fractures from minor falls and my bone density scores are low.
Exclusion Criteria
I have a history of heart disease but my recent ECG is normal or not concerning.
I have a condition affecting my intestines, such as celiac disease or Crohn's.
I have a new, untreated hormone gland disorder.
+21 more
Participant Groups
The study tests if romosozumab improves bone mass in premenopausal women with osteoporosis better than teriparatide does. It involves giving participants romosozumab monthly for a year followed by denosumab every six months for another year, comparing their results to historical controls.
1Treatment groups
Experimental Treatment
Group I: Romosozumab followed by denosumabExperimental Treatment2 Interventions
Romosozumab 210 mg subcutaneous injection, once a month for 12 months followed by denosumab 60 mg subcutaneous injection, once every six months for 12 months.
Denosumab is already approved in European Union, United States, Canada, Japan for the following indications:
πͺπΊ Approved in European Union as Prolia for:
- Osteoporosis in postmenopausal women
- Bone loss associated with hormone ablation therapy for prostate cancer
- Bone loss associated with hormone ablation therapy for breast cancer
πΊπΈ Approved in United States as Prolia for:
- Treatment of postmenopausal women with osteoporosis at high risk for fracture
- Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
- Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer
π¨π¦ Approved in Canada as Prolia for:
- Treatment of osteoporosis in postmenopausal women at high risk for fracture
- Treatment to increase bone mass in men with osteoporosis at high risk for fracture
π―π΅ Approved in Japan as Prolia for:
- Treatment of osteoporosis in postmenopausal women
- Treatment of bone loss associated with hormone ablation therapy for prostate cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Columbia University Irving Medical CenterNew York, NY
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Who Is Running the Clinical Trial?
Columbia UniversityLead Sponsor
AmgenIndustry Sponsor
References
FRAME Study: The Foundation Effect of Building Bone With 1 Year of Romosozumab Leads to Continued Lower Fracture Risk After Transition to Denosumab. [2019]Romosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption. In FRActure study in postmenopausal woMen with ostEoporosis (FRAME), postmenopausal women with osteoporosis received romosozumab 210 mg s.c. or placebo once monthly for 12 months, followed by denosumab 60 mg s.c. once every 6 months in both groups for 12 months. One year of romosozumab increased spine and hip BMD by 13% and 7%, respectively, and reduced vertebral and clinical fractures with persistent fracture risk reduction upon transition to denosumab over 24 months. Here, we further characterize the BMD gains with romosozumab by quantifying the percentages of patients who responded at varying magnitudes; report the mean T-score changes from baseline over the 2-year study and contrast these results with the long-term BMD gains seen with denosumab during Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) and its Extension studies; and assess fracture incidence rates in year 2, when all patients received denosumab. Among 7180 patients (n = 3591 placebo, n = 3589 romosozumab), most romosozumab-treated patients experienced β₯3% gains in BMD from baseline at month 12 (spine, 96%; hip, 78%) compared with placebo (spine, 22%; hip, 16%). For romosozumab patients, mean absolute T-score increases at the spine and hip were 0.88 and 0.32, respectively, at 12 months (placebo: 0.03 and 0.01) and 1.11 and 0.45 at 24 months (placebo-to-denosumab: 0.38 and 0.17), with the 2-year gains approximating the effect of 7 years of continuous denosumab administration. Patients receiving romosozumab versus placebo in year 1 had significantly fewer vertebral fractures in year 2 (81% relative reduction; p
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.
Comparison of romosozumab versus denosumab treatment on bone mineral density after 1 year in rheumatoid arthritis patients with severe osteoporosis: A randomized clinical pilot study. [2023]To investigate the effect of romosozumab versus denosumab treatment on bone mineral density (BMD), disease activity, and joint damage in patients with rheumatoid arthritis and severe osteoporosis.
[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.
Romosozumab and Sequential Therapy in Postmenopausal Osteoporosis. [2021]OBJECTIVE: To review and summarize studies on the effects of romosozumab as sequential therapy for improvements in bone turnover markers, bone mineral density (BMD), and clinical fracture in postmenopausal (PMP) women.<br/> DATA SOURCES: A search of PubMed (1966-August 2019) and International Pharmaceutical Abstracts (1970-August 2019) was conducted using the MeSH and key word term romosozumab and limited to controlled clinical trials.<br/> STUDY SELECTION AND DATA EXTRACTION: An initial review yielded 12 articles. Articles that did not evaluate use of romosozumab before or after another osteoporosis treatment were excluded. Five articles that evaluated the effects of sequential treatment with romosozumab in PMP women on bone turnover markers, bone mineral density, and fracture were included in the final review.<br/> DATA SYNTHESIS: Romosozumab is a humanized, monoclonal antibody that increases bone formation and reduces bone resorption via inhibition of sclerostin. This inhibition stimulates signaling pathways resulting in increased bone formation, reduced bone resorption and increases in BMD. Romosozumab is indicated for the treatment of osteoporosis in PMP women who are at high risk for fracture and failed or cannot take other treatments. The current evidence describing the controlled clinical trials that evaluated use of romosozumab in sequence with other therapies for treatment of PMP osteoporosis is summarized.<br/> CONCLUSION: An evaluation of studies where romosozumab was used in sequence to other therapies in PMP women showed that it causes significant reductions in bone resorption markers, increases in bone-formation markers, improves BMD, and reduces the risk of clinical fracture. However, these efficacy improvements must be carefully weighed against the increased risk of cardiovascular adverse effects compared with other treatments.
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: 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.
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 Agent in the Treatment for Postmenopausal Osteoporosis. [2021]Objective: To review the safety and efficacy of romosozumab (Evenity) in the treatment of osteoporosis in women. Data Sources: An English-language search of PubMed and Medline (1966 to August 2020) was conducted using the keywords romosozumab, sclerostin inhibitor, AMG785, and osteoporosis. Manufacturer prescribing information, abstracts, fda.gov, and ClinicalTrials.gov data were incorporated for additional materials. In addition, a review of bibliographies of retrieved articles was performed to identify additional references. Study Selection/Data Extraction: Articles selected included those that described clinical studies of pharmacokinetics, efficacy, or safety of romosozumab. Data Synthesis: Romosozumab is a human monoclonal antibody that inhibits the action of sclerostin and is the first agent in its class to reach Phase III trials. Significant increases in bone mineral density and decreases in vertebral and hip fractures are demonstrated in Phase III trials. Favorable results led to its marketing approval in several countries. Major adverse cardiac events were observed in one clinical trial. Other adverse effects include arthralgia, headache, and injection site reactions. Place in Therapy: Romosozumab is the first agent to inhibit bone resorption and stimulate bone formation. Romosozumab should be reserved for postmenopausal women at highest risk for fracture and should be followed by an anti-resportive agent to maintain or further increase bone mineral density. This injectable agent should not be considered for women with a history of or at high risk of cardiovascular disease.
[Sequential treatment of osteoporosis with anti-sclerostin.] [2019]Romosozumab is a humanized anti-sclerostin monoclonal antibody that has just been approved for the treatment of osteoporosis in Japan. Romosozumab causes both transient stimulation of bone formation and continuous suppression of resorption, thereby increasing bone mineral density and decreasing fracture incidence. Because the effect of romosozumab is reversible, sequential therapy with anti-resorptives after romosozumab will be necessary. This overview summarizes the results of ARCH study demonstrating superior efficacy of romosozumab compared to alendronate and effect of sequential therapy with alendronate. Possible adverse effect of romosozumab on cardiovascular diseases will also be discussed.
[Romosozumab : a new treatment for severe osteoporosis]. [2021]Romosozumab is a monoclonal antibody against sclerostin. Its dual effect on bone is to increase formation and decrease resorption. Sub-cutaneous injections of romosozumab are administered monthly for one year and must be relayed with a bone resorption inhibitor. Romosozumab followed by denosumab is associated with high increase of bone mineral density and decrease of fragility fractures. Gain of bone mineral density and reduction of fragility fractures are more important with romosozumab as compared with alendronate. The increase in bone mineral density is higher with romosozumab as compared to teriparatide in patients previously treated with alendronate. The use of romosozumab (Evenity) is admitted for patients with high risk of fractures but without serious vascular events.
Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double-Blind, Phase 2, Parallel Group Study. [2019]Over 12 months, romosozumab increased bone formation and decreased bone resorption, resulting in increased bone mineral density (BMD) in postmenopausal women with low BMD (NCT00896532). Herein, we report the study extension evaluating 24 months of treatment with romosozumab, discontinuation of romosozumab, alendronate followed by romosozumab, and romosozumab followed by denosumab. Postmenopausal women aged 55 to 85 years with a lumbar spine (LS), total hip (TH), or femoral neck T-score β€-2.0 and β₯-3.5 were enrolled and randomly assigned to placebo, one of five romosozumab regimens (70 mg, 140 mg, 210 mg monthly [QM]; 140 mg Q3M; 210 mg Q3M) for 24 months, or open-label alendronate for 12 months followed by romosozumab 140 mg QM for 12 months. Eligible participants were then rerandomized 1:1 within original treatment groups to placebo or denosumab 60 mg Q6M for an additional 12 months. Percentage change from baseline in BMD and bone turnover markers (BTMs) at months 24 and 36 and safety were evaluated. Of 364 participants initially randomized to romosozumab, placebo, or alendronate, 315 completed 24 months of treatment and 248 completed the extension. Romosozumab markedly increased LS and TH BMD through month 24, with largest gains observed with romosozumab 210 mg QM (LS = 15.1%; TH = 5.4%). Women receiving romosozumab who transitioned to denosumab continued to accrue BMD, whereas BMD returned toward pretreatment levels with placebo. With romosozumab 210 mg QM, bone formation marker P1NP initially increased after treatment initiation and gradually decreased to below baseline by month 12, remaining below baseline through month 24; bone resorption marker Ξ²-CTX rapidly decreased after treatment, remaining below baseline through month 24. Transition to denosumab further decreased both BTMs, whereas after transition to placebo, P1NP returned to baseline and Ξ²-CTX increased above baseline. Adverse events were balanced between treatment groups through month 36. These data suggest that treatment effects of romosozumab are reversible upon discontinuation and further augmented by denosumab. Β© 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.