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

Postmenopausal Osteoporosis Clinical Trial

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)

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
• 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
• 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.

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal
• Postmenopausal Osteoporosis

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