Efficacy of Romosozumab and Denosumab Combined Treatment in Postmenopausal Osteoporosis Patients with Multiple Fragility Fractures

NCT06720350 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: MAROP.ROM.DEN
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this clinical trial is to investigate the effectiveness of romosozumab started without stopping denosumab in patients diagnosed with postmenopausal osteoporosis with a very high risk of fragility fractures and who is under at least 2 years of denosumab treatment. The main questions aimed to answer are:

• Does it effective to prevent fractures add Romosozumab to ongoing denosumab treatment?
• If it is appropiate to quit denosumab for starting 1 year romosozumab treatment?
• If there is complications in denosumab and romosozumab combination treatment? Researchers will compare the Romosozumab 210mg subcutaneous(sc) monthly plus denosumab 60mg per 6 months sc treatment to prooceeding denosumab treatment and romosozumab 210mg monthly treatment in patient whom denosumab cessaced. Participians are postmenopousal women with osteoporosis and they are under at least 2 years of treatment with denosumab and they will:
• Add 210 mg monthly romosozumab sc injection or switch to 210 mg monthly romosozumab sc injection or proceed 60mg per 6 months denosumab sc injection
• Visit the clinic at least once every 3 months and first month of new treatment regimen, blood tests per 3 months and Bone mineral density examination per 6 months
• Keep a diary of their symptoms

Conditions

Osteoporosis in Post-menopausal Women

Keywords

Osteoporosis; Combination Therapy; Romosozumab; Denosumab

Outcome Measures

Primary Outcomes (2)

• New Fracture

  If the patient exposed new fracture along treatment period

  1 year and 9 months

• Bone Mineral Density

  Bone mineral density before treatment regimen and after treatment done

  1 year

Secondary Outcomes (2)

• New fracture at long term follow up

  5 years

• Beta Crosslaps

  6 months interval

Study Arms (3)

Romosozumab and denosumab combination

EXPERIMENTAL

Romosozumab 210 mg subcutaneously per month combined with denosumab 60mg subcutaneously per 6 months

Drug: Romosozumab and Denosumab Combination Therapy

Romosozumab

ACTIVE COMPARATOR

Romosozumab 210 mg subcutaneously per month

Drug: Romosozumab Prefilled Syringe [Evenity]

Denosumab

ACTIVE COMPARATOR

denosumab 60mg subcutaneously per 6 months

Drug: Denosumab (Prolia)

Interventions

Romosozumab and Denosumab Combination Therapy DRUG

Romosozumab 210mg per month and denosumab 60mg per 6 months will be applied

Romosozumab and denosumab combination

Romosozumab Prefilled Syringe [Evenity] DRUG

Romosozumab 210mg subcutaneously per month

Romosozumab

Denosumab (Prolia) DRUG

Denosumab 60 mg subcutaneously per 6 months

Denosumab

Eligibility Criteria

• Age: 55 Years - 85 Years
• Gender Eligibility Details: Postmenopausal women aged 55-85 years old
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal Women
• Patients with Osteoporosis
• Patients aged between 55 and 85 years old

You may not qualify if:

• Patient with history of Serebrovascular diseases
• Patient with history of Miyocardial Infarction
• Patients who have calcium metabiolism disturbances
• Patients with chronic kidney diseases
• Patient with history of allergic reactions to denosumab or romosozumab

Sponsors & Collaborators

• Marmara University: lead

Study Sites (1)

Marmara University

Istanbul, Turkey (Türkiye)

Location

Related Publications (18)

• Adami G, Pedrollo E, Rossini M, Fassio A, Braga V, Pasetto E, Pollastri F, Benini C, Viapiana O, Gatti D. Romosozumab added to ongoing denosumab in postmenopausal osteoporosis, a prospective observational study. JBMR Plus. 2024 Feb 7;8(4):ziae016. doi: 10.1093/jbmrpl/ziae016. eCollection 2024 Apr.

  PMID: 38544922 BACKGROUND

• Krikelis M, Gazi S, Trovas G, Makris K, Chronopoulos E, Tournis S. Progression of multiple vertebral fractures after denosumab discontinuation under treatment with romosozumab. A case-report. Joint Bone Spine. 2024 Sep;91(5):105754. doi: 10.1016/j.jbspin.2024.105754. Epub 2024 Jun 26.

  PMID: 38942353 BACKGROUND

• Kashii M, Ebina K, Kitaguchi K, Yoshikawa H. Romosozumab was not effective in preventing multiple spontaneous clinical vertebral fractures after denosumab discontinuation: A case report. Bone Rep. 2020 Jun 5;13:100288. doi: 10.1016/j.bonr.2020.100288. eCollection 2020 Dec.

  PMID: 32548215 BACKGROUND

• Langdahl BL, Libanati C, Crittenden DB, Bolognese MA, Brown JP, Daizadeh NS, Dokoupilova E, Engelke K, Finkelstein JS, Genant HK, Goemaere S, Hyldstrup L, Jodar-Gimeno E, Keaveny TM, Kendler D, Lakatos P, Maddox J, Malouf J, Massari FE, Molina JF, Ulla MR, Grauer A. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. Lancet. 2017 Sep 30;390(10102):1585-1594. doi: 10.1016/S0140-6736(17)31613-6. Epub 2017 Jul 26.

  PMID: 28755782 BACKGROUND

• McClung MR, Bolognese MA, Brown JP, Reginster JY, Langdahl BL, Shi Y, Timoshanko J, Libanati C, Chines A, Oates MK. Skeletal responses to romosozumab after 12 months of denosumab. JBMR Plus. 2021 Jun 3;5(7):e10512. doi: 10.1002/jbm4.10512. eCollection 2021 Jul.

  PMID: 34258507 BACKGROUND

• Leder BZ, Tsai JN, Uihlein AV, Wallace PM, Lee H, Neer RM, Burnett-Bowie SA. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet. 2015 Sep 19;386(9999):1147-55. doi: 10.1016/S0140-6736(15)61120-5. Epub 2015 Jul 2.

  PMID: 26144908 BACKGROUND

• Brown JP, Engelke K, Keaveny TM, Chines A, Chapurlat R, Foldes AJ, Nogues X, Civitelli R, De Villiers T, Massari F, Zerbini CAF, Wang Z, Oates MK, Recknor C, Libanati C. Romosozumab improves lumbar spine bone mass and bone strength parameters relative to alendronate in postmenopausal women: results from the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial. J Bone Miner Res. 2021 Nov;36(11):2139-2152. doi: 10.1002/jbmr.4409. Epub 2021 Aug 10.

  PMID: 34190361 BACKGROUND

• Reid IR, Billington EO. Drug therapy for osteoporosis in older adults. Lancet. 2022 Mar 12;399(10329):1080-1092. doi: 10.1016/S0140-6736(21)02646-5.

  PMID: 35279261 BACKGROUND

• Shoback D, Rosen CJ, Black DM, Cheung AM, Murad MH, Eastell R. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgaa048. doi: 10.1210/clinem/dgaa048.

  PMID: 32068863 BACKGROUND

• Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12;377(15):1417-1427. doi: 10.1056/NEJMoa1708322. Epub 2017 Sep 11.

  PMID: 28892457 BACKGROUND

• Kendler DL, Marin F, Zerbini CAF, Russo LA, Greenspan SL, Zikan V, Bagur A, Malouf-Sierra J, Lakatos P, Fahrleitner-Pammer A, Lespessailles E, Minisola S, Body JJ, Geusens P, Moricke R, Lopez-Romero P. Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet. 2018 Jan 20;391(10117):230-240. doi: 10.1016/S0140-6736(17)32137-2. Epub 2017 Nov 9.

  PMID: 29129436 BACKGROUND

• Barrionuevo P, Kapoor E, Asi N, Alahdab F, Mohammed K, Benkhadra K, Almasri J, Farah W, Sarigianni M, Muthusamy K, Al Nofal A, Haydour Q, Wang Z, Murad MH. Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis. J Clin Endocrinol Metab. 2019 May 1;104(5):1623-1630. doi: 10.1210/jc.2019-00192.

  PMID: 30907957 BACKGROUND

• Ayers C, Kansagara D, Lazur B, Fu R, Kwon A, Harrod C. Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-analysis for the American College of Physicians. Ann Intern Med. 2023 Feb;176(2):182-195. doi: 10.7326/M22-0684. Epub 2023 Jan 3.

  PMID: 36592455 BACKGROUND

• Viswanathan M, Reddy S, Berkman N, Cullen K, Middleton JC, Nicholson WK, Kahwati LC. Screening to Prevent Osteoporotic Fractures: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2018 Jun 26;319(24):2532-2551. doi: 10.1001/jama.2018.6537.

  PMID: 29946734 BACKGROUND

• Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2019 May 1;104(5):1595-1622. doi: 10.1210/jc.2019-00221.

  PMID: 30907953 BACKGROUND

• Porter JL, Varacallo MA. Osteoporosis(Archived). 2023 Aug 4. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK441901/

  PMID: 28722930 BACKGROUND

• Singh S, Dutta S, Khasbage S, Kumar T, Sachin J, Sharma J, Varthya SB. A systematic review and meta-analysis of efficacy and safety of Romosozumab in postmenopausal osteoporosis. Osteoporos Int. 2022 Jan;33(1):1-12. doi: 10.1007/s00198-021-06095-y. Epub 2021 Aug 25.

  PMID: 34432115 BACKGROUND

• Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, Zerbini CA, Milmont CE, Chen L, Maddox J, Meisner PD, Libanati C, Grauer A. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016 Oct 20;375(16):1532-1543. doi: 10.1056/NEJMoa1607948. Epub 2016 Sep 18.

  PMID: 27641143 BACKGROUND

MeSH Terms

Conditions

Osteoporosis

Interventions

romosozumab; Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Canan Sanal, Associate Profesor

  Marmara University Medical School

  STUDY DIRECTOR

Central Study Contacts

Muhammed Selim Eryılmaz, Resident

CONTACT

+905424848329; selimerylmz@gmail.com

Canan Şanal, Associate Profesor

CONTACT

+905331381032; canansanal@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each of treatment options will randomized in patients with postmenopausal women.

Study Record Dates

• First Submitted: December 3, 2024
• First Posted: December 6, 2024
• Study Start: January 15, 2025
• Primary Completion (Estimated): October 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: December 27, 2024

Record last verified: 2024-12

Locations

TU (1)