Clinical trial NCT04934072: A Study to Evaluate the Efficacy, Pharmacodynamics, Safety, and Immunogenicity of FKS518 in Postmenopausal Women With Osteoporosis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postmenopausal Osteoporosis
Keywords: Postmenopausal Osteoporosis
FKS518
Denosumab
US-licensed Prolia
Lead sponsor: Fresenius Kabi SwissBioSim GmbH
Sponsor class: INDUSTRY
First posted: 2021-06-22
Enrollment: 553
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage Change From Baseline in LS-BMD by DXA
timeFrame: Baseline and Week 52
Secondary outcomes:
measure: Area Under the Effect Curve (AUEC) of Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)
timeFrame: Baseline to Week 26
measure: Percentage Change From Baseline in BMD at Femoral Neck and Total Hip by DXA
timeFrame: Baseline and Week 52
measure: Percentage Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
timeFrame: Baseline and Week 52 pre dose
measure: Percentage Change From Baseline in Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)
timeFrame: Baseline and Week 52 pre dose
measure: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
timeFrame: Day 1 to Week 78
measure: Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE)
timeFrame: Day 1 to Week 78
measure: Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI)
timeFrame: Day 1 to Week 78
measure: Number of Participants Who Experienced an Injection Site Reaction (ISR)
timeFrame: Day 1 to Week 78
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Diagnostic Consultative Center Aleksandrovska
state: Sofia City
city: Sofia
country: Bulgaria
facility: Diagnostic Consultative Center (DCC) 17 - Sofia
state: Sofia City
city: Sofia
country: Bulgaria
facility: Medical Center N. I. Pirogov
state: Sofia City
city: Haskovo
country: Bulgaria
facility: Medical Center Hipokrat 2000 OOD
city: Pleven
country: Bulgaria
facility: Medical Center Medconsult Pleven
city: Plovdiv
country: Bulgaria
facility: Palmed University Multidisciplinary Hospital for Active Treatment
city: Plovdiv
country: Bulgaria
facility: University Multi-profile Hospital for Active Treatment - Plovdiv
city: Ruse
country: Bulgaria
facility: Medical Center - Teodora EOOD
city: Sliven
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Hadzhi Dimitar
city: Sofia
country: Bulgaria
facility: Lyulin Hospital
city: Varna
country: Bulgaria
facility: Diagnostic and Consultative Center Equita
city: Vidin
country: Bulgaria
facility: Medical Center Sanador M
city: Brno
country: Czechia
facility: CCR Brno
state: Jihormoravsky Kraj
city: Ostrava
country: Czechia
facility: CCR Ostrava
state: Severomoravsky Kraj
city: Uherské Hradiště
country: Czechia
facility: Medical Plus
state: South Moravian
city: Olomouc
country: Czechia
facility: G-Centrum Olomouc s.r.o
city: Ostrava-T?ebovice
country: Czechia
facility: Artroscan
city: Uherské Hradiště
country: Czechia
facility: Medical Plus
city: Tallinn
country: Estonia
facility: Center for Clinical and Basic Research AS - Tallinn
state: Harjumaa
city: Tallinn
country: Estonia
facility: Sihtasutus Pohja-Eesti Regionaalhaigla
state: Harjumaa
city: Parnu
country: Estonia
facility: KLV Arstikabinet
state: Parnumaa
city: Tartu
country: Estonia
facility: Tartu Ulikooli Kliinikum
state: Tartumaa
city: Parnu
country: Estonia
facility: KLV Arstikabinet
city: Tbilisi
country: Georgia
facility: Evex Hospitals - Caraps Medline
state: Borjomi
city: Tbilisi
country: Georgia
facility: Georgian-Dutch Hospital
state: Borjomi
city: Tbilisi
country: Georgia
facility: Hepatology Clinic Hepa
city: Tbilisi
country: Georgia
facility: Tbilisi Heart And Vascular Clinic Ltd
city: Tbilisi
country: Georgia
facility: Jerarsi Clinic
city: Tbilisi
country: Georgia
facility: Raymann - Clinic of Raymann Doctors
city: Tbilisi
country: Georgia
facility: MedCity Ltd.
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar
state: Csongrad
city: Szentes
country: Hungary
facility: Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz
state: Csongrad
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar
state: Csongr
city: Debrecen
country: Hungary
facility: Szent Anna Magan N?gyogyaszati
state: Hajdu-Bihar County
city: Eger
country: Hungary
facility: Markhot Ferenc Oktatokorhaz es Rendel?intezet
state: Heves
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz
state: Pest
city: Zalaegerszeg
country: Hungary
facility: Obudai Egeszsegugyi Centrum
state: Zala
city: Balatonfured
country: Hungary
facility: Drug Research Center Balatonfured
city: Budapest
country: Hungary
facility: Revita Rendel?
city: Budapest
country: Hungary
facility: Clinexpert Gyogycentrum
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum
city: Budapest
country: Hungary
facility: Semmelweis Egyetem - I. sz. Belgyogyaszati Klinika
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont Kenezy Gyula Campus
city: Eger
country: Hungary
facility: Markhot Ferenc Oktatokorhaz es Rendel?intezet
city: Kalocsa
country: Hungary
facility: Kalocsai Szent Kereszt Korhaz
city: Szekesfehervar
country: Hungary
facility: CMed Rehabilitacios es Diagnosztikai Kozpont / Saldinvest Kft.
city: Veszprem
country: Hungary
facility: Vital Medical Center - Reumatologia
city: Wrocław
country: Poland
facility: FutureMeds
state: Dolnoslaskie
city: Wrocław
country: Poland
facility: Wromedica Centrum Zdrowia
state: Dolnoslaskie
city: Wrocław
country: Poland
facility: Centrum Medyczne Oporow
state: Dolnoslaskie
city: Toruń
country: Poland
facility: Nasz Lekarz Przychodnie Medyczne
state: Kujawsko-Pomorskie
city: Krakow
country: Poland
facility: Centrum Medyczne All-Med
state: Malopolskie
city: Krakow
country: Poland
facility: Pratia MCM Krakow
state: Malopolskie
city: Sochaczew
country: Poland
facility: RCMed Oddzial Sochaczew
state: Mazowieckie
city: Warsaw
country: Poland
facility: Centrum Medyczne AMED - Warszawa Targowek
state: Mazowieckie
city: Warsaw
country: Poland
facility: Twoja Przychodnia Szczeci?skie Centrum Medyczne
state: Mazowieckie
city: Warszawa
country: Poland
facility: Medycyna Kliniczna
state: Mazowieckie
city: Warszawa
country: Poland
facility: Rheuma Medicus - Specjalistyczne Centrum Reumatologii i Osteoporozy
state: Mazowieckie
city: Warszawa
country: Poland
facility: SOMED CR - ?od?
state: Mazowieckie
city: Białystok
country: Poland
facility: Osteo-Medic sc dr diabetolog Katarzyna Wasilewska
state: Podlaskie
city: Białystok
country: Poland
facility: ClinicMed
state: Podlaskie
city: Bydgoszcz
country: Poland
facility: Nasz Lekarz O?rodek Bada? Klinicznych - Bydgoszcz
state: Pomorskie
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy
state: Pomorskie
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia - Gdynia
state: Pomorskie
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia - Gdynia
state: Pomorskie
city: Gliwice
country: Poland
facility: Gabinet diagnostyki i leczenia osteoporozy
state: Slaskie
city: Elbląg
country: Poland
facility: Centrum Kliniczno Badawcze J Brzezicki B Górnikiewicz Brzezicka Lekarze
state: Warminsko-Mazurskie
city: Pozna?
country: Poland
facility: Centrum Medyczne Solumed
state: Wielkopolskie
city: Poznan
country: Poland
facility: Centrum Bada? Klinicznych
state: Wielkopolskie
city: Elbląg
country: Poland
facility: Ambulatorium Sp z o.o. - Elblag
state: Zulawy
city: Krakow
country: Poland
facility: Centrum Medyczne All-Med
city: Lodz
country: Poland
facility: SOMED CR - ?od?
city: Nowa Sol
country: Poland
facility: Twoja Przychodnia - Centrum Medyczne Nowa Sol
city: Szczecin
country: Poland
facility: Twoja Przychodnia Szczeci?skie Centrum Medyczne
city: Tomaszow Lubelski
country: Poland
facility: Samodzielny Publiczny Zespo? Opieki Zdrowotnej w Tomaszow Lubelski
city: Warszawa
country: Poland
facility: Klinika Reuma Park sp. z o.o. sp.k - Centrum Medyczne Reuma Park
Study officials:
References: