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

Phase 3

Completed

Conditions: Postmenopausal Osteoporosis

Interventions: Drug: US-licensed Prolia (Amgen)
Drug: FKS518

Registration Number: NCT04934072

Lead Sponsor: Fresenius Kabi SwissBioSim GmbH

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 553

Inclusion Criteria

Not provided

Exclusion Criteria

Disease-related

History and/or presence of 1 severe or >2 moderate vertebral fractures or hip fracture confirmed by x-ray.
Presence of active healing fracture at screening.
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.
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.
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.
Vitamin D deficiency (25-hydroxy vitamin D levels <12 ng/mL) as assessed by central laboratory at screening (retest is allowed once).
Known intolerance to calcium or vitamin D supplements.

Other Medical Conditions
Known or suspected clinically relevant drug hypersensitivity to any components of the study drug, comparable drugs, or to latex.
Renal impairment: creatinine clearance <30 mL/min at screening or receiving dialysis.
Medical evidence of current or history of primary or secondary immunodeficiency.
Infection-related exclusions as further defined in the protocol.
Major surgical procedure within 8 weeks prior to the screening or scheduled during the study.
Current or history of any malignancy, or myeloproliferative, or lymphoproliferative disease within 5 years before screening.
History of clinically significant drug or alcohol abuse within the last year prior to randomization.
Prior denosumab (Prolia, Xgeva, or proposed denosumab biosimilar) exposure.
Prior use of fluoride within the 5 years before inclusion in the study.
Any current or prior use of strontium ranelate.
Any current or prior use of intravenous bisphosphonates.
Current or prior use of teriparatide and other parathormone (PTH) analogues within 12 months before screening.
Current or prior use of systemic oral or transdermal estrogen or selective estrogen receptor modulators or tibolone within 6 months before screening.
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.
Current or prior use of romosozumab or antisclerostin antibody.
Current or prior use of other osteoporotic agents used for the prevention or treatment of osteoporosis.
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.
Concomitant treatment with another biologic drug.
Have received a COVID-19 vaccine within 4 weeks before randomization or COVID-19 vaccination is ongoing at the time of screening.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
US-Prolia	US-licensed Prolia (Amgen)	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.
FKS518	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.

Primary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in LS-BMD by DXA	Baseline and Week 52	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.

Secondary Outcome Measures

Name	Time	Method
Area Under the Effect Curve (AUEC) of Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)	Baseline to Week 26	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.
Percentage Change From Baseline in BMD at Femoral Neck and Total Hip by DXA	Baseline and Week 52	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.
Percentage Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)	Baseline and Week 52 pre dose	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.
Percentage Change From Baseline in Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)	Baseline and Week 52 pre dose	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.
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)	Day 1 to Week 78	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.
Number of Participants Who Experienced a Treatment-Emergent Serious Adverse Event (TESAE)	Day 1 to Week 78	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.
Number of Participants Who Experienced a Treatment-emergent Adverse Event of Special Interest (AESI)	Day 1 to Week 78	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.
Number of Participants Who Experienced an Injection Site Reaction (ISR)	Day 1 to Week 78	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.

Trial Locations

Locations (67): Medical Center Medconsult Pleven
🇧🇬
Pleven, Bulgaria
Hepatology Clinic Hepa
🇬🇪
Tbilisi, Georgia
Tbilisi Heart And Vascular Clinic Ltd
🇬🇪
Tbilisi, Georgia
Jerarsi Clinic
🇬🇪
Tbilisi, Georgia
Raymann - Clinic of Raymann Doctors
🇬🇪
Tbilisi, Georgia
MedCity Ltd.
🇬🇪
Tbilisi, Georgia
Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar
🇭🇺
Szeged, Csongr, Hungary
Medical Center Hipokrat 2000 OOD
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Haskovo, Bulgaria
Palmed University Multidisciplinary Hospital for Active Treatment
🇧🇬
Plovdiv, Bulgaria
CCR Ostrava
🇨🇿
Ostrava, Severomoravsky Kraj, Czechia
Osteo-Medic sc dr diabetolog Katarzyna Wasilewska
🇵🇱
Białystok, Podlaskie, Poland
Diagnostic Consultative Center Aleksandrovska
🇧🇬
Sofia, Sofia City, Bulgaria
Medical Center - Teodora EOOD
🇧🇬
Ruse, Bulgaria
Lyulin Hospital
🇧🇬
Sofia, Bulgaria
Medical Plus
🇨🇿
Uherské Hradiště, Czechia
Diagnostic Consultative Center (DCC) 17 - Sofia
🇧🇬
Sofia, Sofia City, Bulgaria
Medical Center N. I. Pirogov
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Sofia, Sofia City, Bulgaria
Diagnostic and Consultative Center Equita
🇧🇬
Varna, Bulgaria
Medical Center Sanador M
🇧🇬
Vidin, Bulgaria
G-Centrum Olomouc s.r.o
🇨🇿
Olomouc, Czechia
Centrum Kliniczno Badawcze J Brzezicki B Górnikiewicz Brzezicka Lekarze
🇵🇱
Elbląg, Warminsko-Mazurskie, Poland
Ambulatorium Sp z o.o. - Elblag
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Elbląg, Zulawy, Poland
University Multi-profile Hospital for Active Treatment - Plovdiv
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Plovdiv, Bulgaria
Multiprofile Hospital for Active Treatment Hadzhi Dimitar
🇧🇬
Sliven, Bulgaria
CCR Brno
🇨🇿
Brno, Jihormoravsky Kraj, Czechia
Artroscan
🇨🇿
Ostrava-T?ebovice, Czechia
Center for Clinical and Basic Research AS - Tallinn
🇪🇪
Tallinn, Harjumaa, Estonia
Sihtasutus Pohja-Eesti Regionaalhaigla
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Tallinn, Harjumaa, Estonia
KLV Arstikabinet
🇪🇪
Parnu, Estonia
Tartu Ulikooli Kliinikum
🇪🇪
Tartu, Tartumaa, Estonia
Evex Hospitals - Caraps Medline
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Tbilisi, Borjomi, Georgia
Georgian-Dutch Hospital
🇬🇪
Tbilisi, Borjomi, Georgia
Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz
🇭🇺
Szentes, Csongrad, Hungary
Szent Anna Magan N?gyogyaszati
🇭🇺
Debrecen, Hajdu-Bihar County, Hungary
Markhot Ferenc Oktatokorhaz es Rendel?intezet
🇭🇺
Eger, Hungary
Pest Megyei Flor Ferenc Korhaz
🇭🇺
Kistarcsa, Pest, Hungary
Obudai Egeszsegugyi Centrum
🇭🇺
Budapest, Hungary
Drug Research Center Balatonfured
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Balatonfured, Hungary
Revita Rendel?
🇭🇺
Budapest, Hungary
Clinexpert Gyogycentrum
🇭🇺
Budapest, Hungary
Semmelweis Egyetem - I. sz. Belgyogyaszati Klinika
🇭🇺
Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont Kenezy Gyula Campus
🇭🇺
Debrecen, Hungary
Kalocsai Szent Kereszt Korhaz
🇭🇺
Kalocsa, Hungary
CMed Rehabilitacios es Diagnosztikai Kozpont / Saldinvest Kft.
🇭🇺
Szekesfehervar, Hungary
Vital Medical Center - Reumatologia
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Veszprem, Hungary
FutureMeds
🇵🇱
Wrocław, Dolnoslaskie, Poland
Wromedica Centrum Zdrowia
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Wrocław, Dolnoslaskie, Poland
Centrum Medyczne Oporow
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Wrocław, Dolnoslaskie, Poland
Nasz Lekarz Przychodnie Medyczne
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Toruń, Kujawsko-Pomorskie, Poland
Centrum Medyczne All-Med
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Krakow, Poland
Pratia MCM Krakow
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Krakow, Malopolskie, Poland
RCMed Oddzial Sochaczew
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Sochaczew, Mazowieckie, Poland
Centrum Medyczne AMED - Warszawa Targowek
🇵🇱
Warsaw, Mazowieckie, Poland
Twoja Przychodnia Szczeci?skie Centrum Medyczne
🇵🇱
Szczecin, Poland
Medycyna Kliniczna
🇵🇱
Warszawa, Mazowieckie, Poland
Rheuma Medicus - Specjalistyczne Centrum Reumatologii i Osteoporozy
🇵🇱
Warszawa, Mazowieckie, Poland
SOMED CR - ?od?
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Lodz, Poland
ClinicMed
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Białystok, Podlaskie, Poland
Nasz Lekarz O?rodek Bada? Klinicznych - Bydgoszcz
🇵🇱
Bydgoszcz, Pomorskie, Poland
Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy
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Bydgoszcz, Pomorskie, Poland
Centrum Medyczne Pratia - Gdynia
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Gdynia, Pomorskie, Poland
Gabinet diagnostyki i leczenia osteoporozy
🇵🇱
Gliwice, Slaskie, Poland
Centrum Medyczne Solumed
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Pozna?, Wielkopolskie, Poland
Centrum Bada? Klinicznych
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Poznan, Wielkopolskie, Poland
Twoja Przychodnia - Centrum Medyczne Nowa Sol
🇵🇱
Nowa Sol, Poland
Samodzielny Publiczny Zespo? Opieki Zdrowotnej w Tomaszow Lubelski
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Tomaszow Lubelski, Poland
Klinika Reuma Park sp. z o.o. sp.k - Centrum Medyczne Reuma Park
🇵🇱
Warszawa, Poland