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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04934072
Other study ID # FKS518-002
Secondary ID 2020-004422-31
Status Completed
Phase Phase 3
First received
Last updated
Start date July 5, 2021
Est. completion date August 7, 2023

Study information

Verified date August 2023
Source Fresenius Kabi SwissBioSim GmbH
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary objective of this study is to demonstrate equivalent efficacy of FKS518 to US-licensed Prolia in women with postmenopausal osteoporosis (PMO). Participants will be randomized at the beginning of the Double-blind Core Treatment Period (Baseline to Week 52) to receive either FKS518 or US-licensed Prolia on Day 1, and then every 26 weeks for up to 52 weeks. At the beginning of the Double-blind Transition Period (Week 52 to Week 78), participants who received US-licensed Prolia will be re-randomized to either continue receiving US-licensed Prolia every 26 weeks for up to 78 weeks, or switch to receive FKS518 every 26 weeks for up to 78 weeks. Participants who were randomized to receive FKS518 at the beginning of the Double-blind Core Treatment Period will continue to receive this treatment during the Double-blind Transition Period. For Marketing Authorization Application (MAA) in the EU and European Economic Area (EEA) only: The primary objective is to demonstrate equivalent efficacy and pharmacodynamics of the proposed biosimilar denosumab FKS518 to US-Prolia in women with PMO.


Recruitment information / eligibility

Status Completed
Enrollment 553
Est. completion date August 7, 2023
Est. primary completion date August 7, 2023
Accepts healthy volunteers No
Gender Female
Age group 55 Years to 85 Years
Eligibility Inclusion Criteria 1. Female =55 to =85 years of age, inclusive, at screening. 2. Have a body mass index (BMI) =18 to =32 kg/m^2. 3. Participant should have confirmed postmenopausal status, defined as age-related or early/premature amenorrhea =12 consecutive months and increased follicle-stimulating hormone (FSH) >40 mIU/mL at screening; or surgical menopause (bilateral oophorectomy with or without hysterectomy) =12 months prior to screening. 4. Absolute bone mineral density (BMD) consistent with T-score =-2.5 and =-4.0 at the lumbar spine as measured by dual energy x-ray absorptiometry (DXA) as per central assessment. 5. At least 2 vertebrae in the lumbar vertebrae 1 to lumbar vertebrae 4 (L1-L4) region and at least 1 hip joint are evaluable by DXA. 6. Clinically acceptable physical examinations and laboratory tests and no history or evidence of any clinically significant concomitant medical disorder that, in the opinion of the Investigator, would pose a risk to participant safety or interfere with study evaluations or procedures. 7. Written informed consent including accepting a separate Information Sheet containing important information about COVID-19 and its general risks for participants participating in the clinical trial. Exclusion Criteria: Disease-related 1. History and/or presence of 1 severe or >2 moderate vertebral fractures or hip fracture confirmed by x-ray. 2. Presence of active healing fracture at screening. 3. History and/or presence of bone-related disorders, such as but not limited to Paget's disease, osteomalacia, hyperparathyroidism (or parathyroid disorders), or renal osteodystrophy. 4. Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (eg, tooth extraction, dental implants, or oral surgery in the past 6 months), poor oral hygiene, periodontal, and/or pre-existing dental disease as assessed by the Investigator. 5. Evidence of hypocalcemia (albumin-adjusted serum calcium <2.13 mmol/L or <8.5 mg/dL) or hypercalcemia (albumin-adjusted serum calcium >2.6 mmol/L or >10.5 mg/dL) as assessed by the central laboratory at screening. 6. Vitamin D deficiency (25-hydroxy vitamin D levels <12 ng/mL) as assessed by central laboratory at screening (retest is allowed once). 7. Known intolerance to calcium or vitamin D supplements. Other Medical Conditions 8. Known or suspected clinically relevant drug hypersensitivity to any components of the study drug, comparable drugs, or to latex. 9. Renal impairment: creatinine clearance <30 mL/min at screening or receiving dialysis. 10. Medical evidence of current or history of primary or secondary immunodeficiency. 11. Infection-related exclusions as further defined in the protocol. 12. Major surgical procedure within 8 weeks prior to the screening or scheduled during the study. 13. Current or history of any malignancy, or myeloproliferative, or lymphoproliferative disease within 5 years before screening. 14. History of clinically significant drug or alcohol abuse within the last year prior to randomization. 15. Prior denosumab (Prolia, Xgeva, or proposed denosumab biosimilar) exposure. 16. Prior use of fluoride within the 5 years before inclusion in the study. 17. Any current or prior use of strontium ranelate. 18. Any current or prior use of intravenous bisphosphonates. 19. Current or prior use of teriparatide and other parathormone (PTH) analogues within 12 months before screening. 20. Current or prior use of systemic oral or transdermal estrogen or selective estrogen receptor modulators or tibolone within 6 months before screening. 21. Current or prior use of calcitonin or cinacalcet within 3 months before screening or any cathepsin K inhibitor (eg, odanacatib) within 18 months before screening. 22. Current or prior use of romosozumab or antisclerostin antibody. 23. Current or prior use of other osteoporotic agents used for the prevention or treatment of osteoporosis. 24. Current use within 3 months before screening of any medication with known influence on the skeletal system (eg, systemic corticosteroids, heparin, lithium, etc) with exceptions described in the protocol. 25. Concomitant treatment with another biologic drug. 26. Have received a COVID-19 vaccine within 4 weeks before randomization or COVID-19 vaccination is ongoing at the time of screening.

Study Design


Intervention

Drug:
FKS518
Participants will receive FKS518 via subcutaneous injection, every 26 weeks.
US-licensed Prolia
Participants will receive US-licensed Prolia via subcutaneous injection, every 26 weeks.

Locations

Country Name City State
Bulgaria Medical Center Hipokrat 2000 OOD Haskovo
Bulgaria Medical Center Medconsult Pleven Pleven
Bulgaria Palmed University Multidisciplinary Hospital for Active Treatment Plovdiv
Bulgaria University Multi-profile Hospital for Active Treatment - Plovdiv Plovdiv
Bulgaria Medical Center - Teodora EOOD Ruse
Bulgaria Multiprofile Hospital for Active Treatment Hadzhi Dimitar Sliven
Bulgaria Diagnostic Consultative Center (DCC) 17 - Sofia Sofia Sofia City
Bulgaria Diagnostic Consultative Center Aleksandrovska Sofia Sofia City
Bulgaria Lyulin Hospital Sofia
Bulgaria Medical Center N. I. Pirogov Sofia Sofia City
Bulgaria Diagnostic and Consultative Center Equita Varna
Bulgaria Medical Center Sanador M Vidin
Czechia CCR Brno Brno Jihormoravsky Kraj
Czechia G-Centrum Olomouc s.r.o Olomouc
Czechia CCR Ostrava Ostrava Severomoravsky Kraj
Czechia Artroscan Ostrava-T?ebovice
Czechia Medical Plus Uherske Hradi?t?
Czechia Medical Plus Uherske Hradi?t? South Moravian
Estonia KLV Arstikabinet Parnu Parnumaa
Estonia KLV Arstikabinet Parnu
Estonia Center for Clinical and Basic Research AS - Tallinn Tallinn Harjumaa
Estonia Sihtasutus Pohja-Eesti Regionaalhaigla Tallinn Harjumaa
Estonia Tartu Ulikooli Kliinikum Tartu Tartumaa
Georgia Evex Hospitals - Caraps Medline Tbilisi Borjomi
Georgia Georgian-Dutch Hospital Tbilisi Borjomi
Georgia Hepatology Clinic Hepa Tbilisi
Georgia Jerarsi Clinic Tbilisi
Georgia MedCity Ltd. Tbilisi
Georgia Raymann - Clinic of Raymann Doctors Tbilisi
Georgia Tbilisi Heart And Vascular Clinic Ltd Tbilisi
Hungary Drug Research Center Balatonfured Balatonfured
Hungary Clinexpert Gyogycentrum Budapest
Hungary Obudai Egeszsegugyi Centrum Budapest
Hungary Revita Rendel? Budapest
Hungary Semmelweis Egyetem - I. sz. Belgyogyaszati Klinika Budapest
Hungary Debreceni Egyetem Klinikai Kozpont Kenezy Gyula Campus Debrecen
Hungary Szent Anna Magan N?gyogyaszati Debrecen Hajdu-Bihar County
Hungary Markhot Ferenc Oktatokorhaz es Rendel?intezet Eger Heves
Hungary Markhot Ferenc Oktatokorhaz es Rendel?intezet Eger
Hungary Kalocsai Szent Kereszt Korhaz Kalocsa
Hungary Pest Megyei Flor Ferenc Korhaz Kistarcsa Pest
Hungary Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar Szeged Csongr
Hungary Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar Szeged Csongrad
Hungary CMed Rehabilitacios es Diagnosztikai Kozpont / Saldinvest Kft. Szekesfehervar
Hungary Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz Szentes Csongrad
Hungary Vital Medical Center - Reumatologia Veszprem
Hungary Obudai Egeszsegugyi Centrum Zalaegerszeg Zala
Poland ClinicMed Bia?ystok Podlaskie
Poland ZDROWIE Osteo-Medic s.c. L. I A. Racewicz, A. i J. Supronik Bia?ystok Podlaskie
Poland Nasz Lekarz O?rodek Bada? Klinicznych - Bydgoszcz Bydgoszcz Pomorskie
Poland Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy Bydgoszcz Pomorskie
Poland Ambulatorium Sp z o.o. - Elbl?g Elbl?g ?u?awy
Poland Centrum Kliniczno Badawcze J Brzezicki B Gornikiewicz Brzezicka Lekarze Spo?ka Partnerska Elbl?g Warminsko-Mazurskie
Poland Centrum Medyczne Pratia - Gdynia Gdynia Pomorskie
Poland Centrum Medyczne Pratia - Gdynia Gdynia Pomorskie
Poland Gabinet diagnostyki i leczenia osteoporozy Gliwice Slaskie
Poland Centrum Medyczne All-Med Krakow
Poland Centrum Medyczne All-Med Krakow Malopolskie
Poland Pratia MCM Krakow Krakow Malopolskie
Poland SOMED CR - ?od? Lodz
Poland Twoja Przychodnia - Centrum Medyczne Nowa Sol Nowa Sol
Poland Centrum Medyczne Solumed Pozna? Wielkopolskie
Poland Centrum Bada? Klinicznych Poznan Wielkopolskie
Poland RCMed Oddzial Sochaczew Sochaczew Mazowieckie
Poland Twoja Przychodnia Szczeci?skie Centrum Medyczne Szczecin
Poland Samodzielny Publiczny Zespo? Opieki Zdrowotnej w Tomaszow Lubelski Tomaszow Lubelski
Poland Nasz Lekarz Przychodnie Medyczne Toru? Kujawsko-Pomorskie
Poland Centrum Medyczne AMED - Warszawa Targowek Warsaw Mazowieckie
Poland Twoja Przychodnia Szczeci?skie Centrum Medyczne Warsaw Mazowieckie
Poland Klinika Reuma Park sp. z o.o. sp.k - Centrum Medyczne Reuma Park Warszawa
Poland Medycyna Kliniczna Warszawa Mazowieckie
Poland SOMED CR - ?od? Warszawa Mazowieckie
Poland Rheuma Medicus - Specjalistyczne Centrum Reumatologii i Osteoporozy Warszawa-Ochota Mazowieckie
Poland Centrum Medyczne Oporow Wroc?aw Dolnoslaskie
Poland FutureMeds Wroc?aw Dolnoslaskie
Poland Wromedica Centrum Zdrowia Wroc?aw Dolnoslaskie

Sponsors (1)

Lead Sponsor Collaborator
Fresenius Kabi SwissBioSim GmbH

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Estonia,  Georgia,  Hungary,  Poland, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage Change from Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) by Dual Energy X-ray Absorptiometry (DXA) at Week 52 Baseline (Screening) to Week 52
Primary Area Under the Effect Curve (AUEC) of Serum C-terminal Cross-Linking Telopeptide of Type 1 Collagen (CTX) at Week 26 Baseline (Day 1) to Week 26
Secondary Percentage Change from Baseline in Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX) at Week 52 Baseline (Day 1) to Week 52
Secondary Percentage Change from Baseline in Bone Mineral Density (BMD) at Femoral Neck and Total Hip by Dual Energy X-ray Absorptiometry (DXA) at Week 52 Baseline (Screening) to Week 52
Secondary Percentage Change from Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) at Week 52 Baseline (Day 1) to Week 52
Secondary Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) Day 1 to Week 78
Secondary Number of Participants Who Experience a Serious Adverse Event (SAE) Day 1 to Week 78
Secondary Number of Participants Who Experience a Treatment-emergent Adverse Event of Special Interest (AESI) A Treatment-emergent Adverse Event of Special Interest (AESI) is defined as drug-related hypersensitivity/allergic reactions (Common Terminology Criteria for Adverse Events [CTCAE] Grade =3 or reported as serious adverse events [SAEs]) and adverse events (AEs) leading to investigational product (IP) discontinuation or study withdrawal. Day 1 to Week 78
Secondary Number of Participants Who Experience an Injection Site Reaction (ISR) Day 1 to Week 56
Secondary Number of Participants With Antidrug Antibodies (ADAs) 4 weeks prior to first drug administration to Week 78
Secondary Number of Participants With Antidrug Antibody (ADA) Titers 4 weeks prior to first drug administration to Week 78
Secondary Number of Participants With Neutralizing Antibodies (NAb) 4 weeks prior to first drug administration to Week 78
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