A Study to Evaluate the Efficacy, Pharmacodynamics, Safety, and Immunogenicity of FKS518 in Postmenopausal Women With Osteoporosis

A Double-blind, Randomized, Multicenter, Multiple-dose, 2-arm, Parallel-group Study to Evaluate Efficacy, Pharmacodynamics, Safety, and Immunogenicity of FKS518 - Proposed Biosimilar to Denosumab With Prolia® in Postmenopausal Women With Osteoporosis (LUMIADE-3 Study)

The primary objective of this study is to demonstrate equivalent efficacy of the proposed biosimilar denosumab FKS518 to US-licensed Prolia in women with postmenopausal osteoporosis (PMO).

Study Overview

• Status: Completed
• Conditions: Postmenopausal Osteoporosis
• Intervention / Treatment: Drug: FKS518; Drug: US-licensed Prolia (Amgen)

• Study Type: Interventional
• Enrollment (Actual): 553
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Haskovo, Bulgaria, 6300
    • Medical Center Hipokrat 2000 OOD
  • Pleven, Bulgaria, 5800
    • Medical Center Medconsult Pleven
  • Plovdiv, Bulgaria, 4002
    • Palmed University Multidisciplinary Hospital for Active Treatment
  • Plovdiv, Bulgaria, 4003
    • University Multi-profile Hospital for Active Treatment - Plovdiv
  • Ruse, Bulgaria, 7012
    • Medical Center - Teodora EOOD
  • Sliven, Bulgaria, 8800
    • Multiprofile Hospital for Active Treatment Hadzhi Dimitar
  • Sofia, Bulgaria, 1336
    • Lyulin Hospital
  • Varna, Bulgaria, 9002
    • Diagnostic and Consultative Center Equita
  • Vidin, Bulgaria, 3703
    • Medical Center Sanador M
  • Sofia City
    • Sofia, Sofia City, Bulgaria, 1431
      • Diagnostic Consultative Center Aleksandrovska
    • Sofia, Sofia City, Bulgaria, 1505
      • Diagnostic Consultative Center (DCC) 17 - Sofia
    • Sofia, Sofia City, Bulgaria, 1612
      • Medical Center N. I. Pirogov
• Czechia
  • Olomouc, Czechia, 772 00
    • G-Centrum Olomouc s.r.o
  • Ostrava-T?ebovice, Czechia, 722 00
    • Artroscan
  • Uherské Hradiště, Czechia, 686 01
    • Medical Plus
  • Jihormoravsky Kraj
    • Brno, Jihormoravsky Kraj, Czechia, 602 00
      • CCR Brno
  • Severomoravsky Kraj
    • Ostrava, Severomoravsky Kraj, Czechia, 702 00
      • CCR Ostrava
  • South Moravian
    • Uherské Hradiště, South Moravian, Czechia, 686 01
      • Medical Plus
• Estonia
  • Parnu, Estonia, 80010
    • KLV Arstikabinet
  • Harjumaa
    • Tallinn, Harjumaa, Estonia, 10128
      • Center for Clinical and Basic Research AS - Tallinn
    • Tallinn, Harjumaa, Estonia, 13419
      • Sihtasutus Pohja-Eesti Regionaalhaigla
  • Parnumaa
    • Parnu, Parnumaa, Estonia, 80010
      • KLV Arstikabinet
  • Tartumaa
    • Tartu, Tartumaa, Estonia, 50406
      • Tartu Ulikooli Kliinikum
• Georgia
  • Tbilisi, Georgia, 0167
    • Jerarsi Clinic
  • Tbilisi, Georgia, 0159
    • Tbilisi Heart and Vascular Clinic Ltd
  • Tbilisi, Georgia, 0159
    • Hepatology Clinic Hepa
  • Tbilisi, Georgia, 0186
    • Raymann - Clinic of Raymann Doctors
  • Tbilisi, Georgia, 186
    • MedCity Ltd.
  • Borjomi
    • Tbilisi, Borjomi, Georgia, 0159
      • Evex Hospitals - Caraps Medline
    • Tbilisi, Borjomi, Georgia, 0172
      • Georgian-Dutch hospital
• Hungary
  • Balatonfured, Hungary, 8230
    • Drug Research Center Balatonfured
  • Budapest, Hungary, 1036
    • Óbudai Egészségügyi Centrum
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem - I. sz. Belgyógyászati Klinika
  • Budapest, Hungary, 1027
    • Revita Rendel?
  • Budapest, Hungary, 1033
    • Clinexpert Gyogycentrum
  • Debrecen, Hungary, 4031
    • Debreceni Egyetem Klinikai Központ Kenézy Gyula Campus
  • Eger, Hungary, 3300
    • Markhot Ferenc Oktatokorhaz es Rendel?intezet
  • Kalocsa, Hungary, 6300
    • Kalocsai Szent Kereszt Korhaz
  • Szekesfehervar, Hungary, 8000
    • CMed Rehabilitacios es Diagnosztikai Kozpont / Saldinvest Kft.
  • Veszprem, Hungary, 8200
    • Vital Medical Center - Reumatológia
  • Csongr
    • Szeged, Csongr, Hungary, 6720
      • Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar
  • Csongrad
    • Szeged, Csongrad, Hungary, 6725
      • Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar
    • Szentes, Csongrad, Hungary, 6600
      • Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz
  • Hajdu-Bihar County
    • Debrecen, Hajdu-Bihar County, Hungary, 4024
      • Szent Anna Magan N?gyogyaszati
  • Heves
    • Eger, Heves, Hungary, 3300
      • Markhot Ferenc Oktatokorhaz es Rendel?intezet
  • Pest
    • Kistarcsa, Pest, Hungary, 2143
      • Pest Megyei Flor Ferenc Korhaz
  • Zala
    • Zalaegerszeg, Zala, Hungary, 8900
      • Óbudai Egészségügyi Centrum
• Poland
  • Krakow, Poland, 31-023
    • Centrum Medyczne ALL-MED
  • Lodz, Poland, 90-368
    • SOMED CR - ?od?
  • Nowa Sol, Poland, 67-100
    • Twoja Przychodnia - Centrum Medyczne Nowa Sol
  • Szczecin, Poland, 71-434
    • Twoja Przychodnia Szczeci?skie Centrum Medyczne
  • Tomaszow Lubelski, Poland, 22-600
    • Samodzielny Publiczny Zespo? Opieki Zdrowotnej w Tomaszow Lubelski
  • Warszawa, Poland, 02-691
    • Klinika Reuma Park sp. z o.o. sp.k - Centrum Medyczne Reuma Park
  • Dolnoslaskie
    • Wrocław, Dolnoslaskie, Poland, 51-685
      • Wromedica Centrum Zdrowia
    • Wrocław, Dolnoslaskie, Poland, 52-416
      • Centrum Medyczne Oporow
    • Wrocław, Dolnoslaskie, Poland, 50-088
      • FutureMeds
  • Kujawsko-Pomorskie
    • Toruń, Kujawsko-Pomorskie, Poland, 87-100
      • Nasz Lekarz Przychodnie Medyczne
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-510
      • Pratia MCM Krakow
    • Krakow, Malopolskie, Poland, 30-033
      • Centrum Medyczne ALL-MED
  • Mazowieckie
    • Sochaczew, Mazowieckie, Poland, 96-500
      • RCMed Oddzial Sochaczew
    • Warsaw, Mazowieckie, Poland, 01-518
      • Centrum Medyczne AMED - Warszawa Targowek
    • Warsaw, Mazowieckie, Poland, 02-777
      • Twoja Przychodnia Szczeci?skie Centrum Medyczne
    • Warszawa, Mazowieckie, Poland, 00-874
      • Medycyna Kliniczna
    • Warszawa, Mazowieckie, Poland, 04-730
      • SOMED CR - ?od?
    • Warszawa, Mazowieckie, Poland, 02-118
      • Rheuma Medicus - Specjalistyczne Centrum Reumatologii i Osteoporozy
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-351
      • Osteo-Medic sc dr diabetolog Katarzyna Wasilewska
    • Białystok, Podlaskie, Poland, 15-879
      • ClinicMed
  • Pomorskie
    • Bydgoszcz, Pomorskie, Poland, 85-065
      • Nasz Lekarz O?rodek Bada? Klinicznych - Bydgoszcz
    • Bydgoszcz, Pomorskie, Poland, 85-168
      • Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy
    • Gdynia, Pomorskie, Poland, 81-338
      • Centrum Medyczne Pratia - Gdynia
    • Gdynia, Pomorskie, Poland, 81-340
      • Centrum Medyczne Pratia - Gdynia
  • Slaskie
    • Gliwice, Slaskie, Poland, 44-122
      • Gabinet diagnostyki i leczenia osteoporozy
  • Warminsko-Mazurskie
    • Elbląg, Warminsko-Mazurskie, Poland, 82-300
      • Centrum Kliniczno Badawcze J Brzezicki B Górnikiewicz Brzezicka Lekarze
  • Wielkopolskie
    • Pozna?, Wielkopolskie, Poland, 60-529
      • Centrum Medyczne Solumed
    • Poznan, Wielkopolskie, Poland, 60-773
      • Centrum Bada? Klinicznych
  • Zulawy
    • Elbląg, Zulawy, Poland, 82-300
      • Ambulatorium Sp z o.o. - Elblag

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FKS518; FKS518 was administered on Day 1, and then every 26 weeks (6 months), i.e., Week 26 and Week 52, at a dose of 60 mg for a total of 3 administrations.	Drug: FKS518; subcutaneously by single-use prefilled syringe (PFS); Other Names: Denosumab biosimilar
Active Comparator: US-Prolia; US-Prolia was administered on Day 1, and then every 26 weeks (6 months), i.e., Week 26 and Week 52, at a dose of 60 mg for a total of 3 administrations.	Drug: US-licensed Prolia (Amgen); subcutaneously by single-use PFS; Other Names: Denosumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in LS-BMD by DXA	Bone density was measured at the lumbar spine from L1 through L4. Per FDA request for this study, data were analyzed by non-inferiority and non-superiority analyses. Decreased BMD is associated with risk of fracture.	Baseline and Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Effect Curve (AUEC) of Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)	Area under the effect curve for the (untransformed) biomarker concentrations from baseline up to Week 26. Any possible rebound effect where biomarker concentrations rose above baseline was not taken into account, and only the area below baseline was considered in this parameter.	Baseline to Week 26
Percentage Change From Baseline in BMD at Femoral Neck and Total Hip by DXA	The proximal femur (inclusive of femoral neck and total hip) DXA scans were obtained from the left side when possible. If the right side had to be used (e.g., due to implants) or was inadvertently used at baseline, then it had to be used consistently throughout the study. Data reported are for one half of the body only.	Baseline and Week 52
Percentage Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)	P1NP is a bone biomarker. Serum samples were collected for analysis of P1NP to evaluate bone formation (P1NP) in response to treatment with FKS518 and US-Prolia. A decrease in the serum levels of P1NP is expected following treatment with denosumab and is suggestive of improvement.	Baseline and Week 52 pre dose
Percentage Change From Baseline in Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)	Serum CTX is a bone biomarker. Serum samples were collected for analysis of CTX to evaluate bone resorption in response to treatment with FKS518 or US-Prolia. A decrease in the serum levels of CTX is expected following treatment with US-Prolia and is suggestive of improvement.	Baseline and Week 52 pre dose
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)	Treatment-emergence was defined as AEs that began or increased in severity or frequency on or after the date of first administration of IP in a given treatment Period (Core or Transition) up to the Early Termination/End of Study Visit.	Day 1 to Week 78
Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE)	Treatment-emergence was defined as SAEs that began or increased in severity or frequency on or after the date of first administration of IP up to the Early Termination/End of Study Visit.	Day 1 to Week 78
Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI)	A Treatment-emergent 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 AEs leading to IP discontinuation or study withdrawal.	Day 1 to Week 78
Number of Participants Who Experienced an Injection Site Reaction (ISR)	Local tolerability in terms of ISRs was assessed by inspection of the skin and appendages in proximity to the site of administration. The injection site was the abdomen, and the IP was injected slowly. This local tolerability assessment was performed by the Investigator or designee to determine the presence of e.g., erythema, rash, tenderness, swelling, itching, bruising, pain, extravasation, phlebitis, or other types of reaction. The Investigator was also requested to ask participants during assessment about any such reactions that may have occurred since last assessment.	Day 1 to Week 78

Collaborators and Investigators

• Sponsor: Fresenius Kabi SwissBioSim GmbH

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2021
• Primary Completion (Actual): August 7, 2023
• Study Completion (Actual): August 7, 2023

Study Registration Dates

• First Submitted: June 3, 2021
• First Submitted That Met QC Criteria: June 14, 2021
• First Posted (Actual): June 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Postmenopausal Osteoporosis; Denosumab; FKS518; US-licensed Prolia
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: FKS518-002; 2020-004422-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No