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

NCT04934072 | Completed Phase 3 Results

• 2 other identifiers: FKS518-0022020-004422-31
• Study Type: interventional
• Target: 553
• Locations: 6 countries
• Sites: 76

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).

Conditions

Postmenopausal Osteoporosis

Keywords

Postmenopausal Osteoporosis; FKS518; Denosumab; US-licensed Prolia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Area Under the Effect Curve (AUEC) of Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)

  Baseline to Week 26

• Percentage Change From Baseline in BMD at Femoral Neck and Total Hip by DXA

  Baseline and Week 52

• Percentage Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)

  Baseline and Week 52 pre dose

• Percentage Change From Baseline in Serum C-terminal Cross-linking Telopeptide of Type 1 Collagen (CTX)

  Baseline and Week 52 pre dose

• Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

  Day 1 to Week 78

Study Arms (2)

FKS518

EXPERIMENTAL

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

US-Prolia

ACTIVE COMPARATOR

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)

Interventions

FKS518 DRUG

subcutaneously by single-use prefilled syringe (PFS)

Also known as: Denosumab biosimilar

FKS518

US-licensed Prolia (Amgen) DRUG

subcutaneously by single-use PFS

Also known as: Denosumab

US-Prolia

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female ≥55 to ≤85 years of age, inclusive, at screening.
• Have a body mass index (BMI) ≥18 to ≤32 kg/m\^2.
• 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.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Fresenius Kabi SwissBioSim GmbH: lead

Study Sites (76)

Diagnostic Consultative Center Aleksandrovska

Sofia, Sofia-Grad, 1431, Bulgaria

Location

Diagnostic Consultative Center (DCC) 17 - Sofia

Sofia, Sofia-Grad, 1505, Bulgaria

Location

Medical Center N. I. Pirogov

Sofia, Sofia-Grad, 1612, Bulgaria

Location

Medical Center Hipokrat 2000 OOD

Haskovo, 6300, Bulgaria

Location

Medical Center Medconsult Pleven

Pleven, 5800, Bulgaria

Location

Palmed University Multidisciplinary Hospital for Active Treatment

Plovdiv, 4002, Bulgaria

Location

University Multi-profile Hospital for Active Treatment - Plovdiv

Plovdiv, 4003, Bulgaria

Location

Medical Center - Teodora EOOD

Rousse, 7012, Bulgaria

Location

Multiprofile Hospital for Active Treatment Hadzhi Dimitar

Sliven, 8800, Bulgaria

Location

Lyulin Hospital

Sofia, 1336, Bulgaria

Location

Diagnostic and Consultative Center Equita

Varna, 9002, Bulgaria

Location

Medical Center Sanador M

Vidin, 3703, Bulgaria

Location

CCR Brno

Brno, Jihormoravsky Kraj, 602 00, Czechia

Location

CCR Ostrava

Ostrava, Severomoravsky Kraj, 702 00, Czechia

Location

Medical Plus

Uherské Hradiště, South Moravian, 686 01, Czechia

Location

G-Centrum Olomouc s.r.o

Olomouc, 772 00, Czechia

Location

Artroscan

Ostrava-T?ebovice, 722 00, Czechia

Location

Medical Plus

Uherské Hradiště, 686 01, Czechia

Location

Center for Clinical and Basic Research AS - Tallinn

Tallinn, Harju, 10128, Estonia

Location

Sihtasutus Pohja-Eesti Regionaalhaigla

Tallinn, Harju, 13419, Estonia

Location

KLV Arstikabinet

Pärnu, Pärnumaa, 80010, Estonia

Location

Tartu Ulikooli Kliinikum

Tartu, Tartu, 50406, Estonia

Location

KLV Arstikabinet

Pärnu, 80010, Estonia

Location

Evex Hospitals - Caraps Medline

Tbilisi, Borjomi, 0159, Georgia

Location

Georgian-Dutch Hospital

Tbilisi, Borjomi, 0172, Georgia

Location

Hepatology Clinic Hepa

Tbilisi, 0159, Georgia

Location

Tbilisi Heart And Vascular Clinic Ltd

Tbilisi, 0159, Georgia

Location

Jerarsi Clinic

Tbilisi, 0167, Georgia

Location

Raymann - Clinic of Raymann Doctors

Tbilisi, 0186, Georgia

Location

MedCity Ltd.

Tbilisi, 186, Georgia

Location

Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar

Szeged, Csongr, 6720, Hungary

Location

Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar

Szeged, Csongrád megye, 6725, Hungary

Location

Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz

Szentes, Csongrád megye, 6600, Hungary

Location

Szent Anna Magan N?gyogyaszati

Debrecen, Hajdú-Bihar, 4024, Hungary

Location

Markhot Ferenc Oktatokorhaz es Rendel?intezet

Eger, Heves County, 3300, Hungary

Location

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, Pest County, 2143, Hungary

Location

Obudai Egeszsegugyi Centrum

Zalaegerszeg, Zala County, 8900, Hungary

Location

Drug Research Center Balatonfured

Balatonfüred, 8230, Hungary

Location

Revita Rendel?

Budapest, 1027, Hungary

Location

Clinexpert Gyogycentrum

Budapest, 1033, Hungary

Location

Obudai Egeszsegugyi Centrum

Budapest, 1036, Hungary

Location

Semmelweis Egyetem - I. sz. Belgyogyaszati Klinika

Budapest, 1083, Hungary

Location

Debreceni Egyetem Klinikai Kozpont Kenezy Gyula Campus

Debrecen, 4031, Hungary

Location

Markhot Ferenc Oktatokorhaz es Rendel?intezet

Eger, 3300, Hungary

Location

Kalocsai Szent Kereszt Korhaz

Kalocsa, 6300, Hungary

Location

CMed Rehabilitacios es Diagnosztikai Kozpont / Saldinvest Kft.

Székesfehérvár, 8000, Hungary

Location

Vital Medical Center - Reumatologia

Veszprém, 8200, Hungary

Location

Centrum Medyczne Solumed

Pozna?, Greater Poland Voivodeship, 60-529, Poland

Location

Centrum Bada? Klinicznych

Poznan, Greater Poland Voivodeship, 60-773, Poland

Location

Nasz Lekarz Przychodnie Medyczne

Torun, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

Location

Centrum Medyczne All-Med

Krakow, Lesser Poland Voivodeship, 30-033, Poland

Location

Pratia MCM Krakow

Krakow, Lesser Poland Voivodeship, 30-510, Poland

Location

FutureMeds

Wroclaw, Lower Silesian Voivodeship, 50-088, Poland

Location

Wromedica Centrum Zdrowia

Wroclaw, Lower Silesian Voivodeship, 51-685, Poland

Location

Centrum Medyczne Oporow

Wroclaw, Lower Silesian Voivodeship, 52-416, Poland

Location

RCMed Oddzial Sochaczew

Sochaczew, Masovian Voivodeship, 96-500, Poland

Location

Medycyna Kliniczna

Warsaw, Masovian Voivodeship, 00-874, Poland

Location

Centrum Medyczne AMED - Warszawa Targowek

Warsaw, Masovian Voivodeship, 01-518, Poland

Location

Rheuma Medicus - Specjalistyczne Centrum Reumatologii i Osteoporozy

Warsaw, Masovian Voivodeship, 02-118, Poland

Location

Twoja Przychodnia Szczeci?skie Centrum Medyczne

Warsaw, Masovian Voivodeship, 02-777, Poland

Location

SOMED CR - ?od?

Warsaw, Masovian Voivodeship, 04-730, Poland

Location

Osteo-Medic sc dr diabetolog Katarzyna Wasilewska

Bialystok, Podlaskie Voivodeship, 15-351, Poland

Location

ClinicMed

Bialystok, Podlaskie Voivodeship, 15-879, Poland

Location

Nasz Lekarz O?rodek Bada? Klinicznych - Bydgoszcz

Bydgoszcz, Pomeranian Voivodeship, 85-065, Poland

Location

Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy

Bydgoszcz, Pomeranian Voivodeship, 85-168, Poland

Location

Centrum Medyczne Pratia - Gdynia

Gdynia, Pomeranian Voivodeship, 81-338, Poland

Location

Centrum Medyczne Pratia - Gdynia

Gdynia, Pomeranian Voivodeship, 81-340, Poland

Location

Gabinet diagnostyki i leczenia osteoporozy

Gliwice, Silesian Voivodeship, 44-122, Poland

Location

Centrum Kliniczno Badawcze J Brzezicki B Górnikiewicz Brzezicka Lekarze

Elblag, Warmian-Masurian Voivodeship, 82-300, Poland

Location

Ambulatorium Sp z o.o. - Elblag

Elblag, Zulawy, 82-300, Poland

Location

Centrum Medyczne All-Med

Krakow, 31-023, Poland

Location

SOMED CR - ?od?

Lodz, 90-368, Poland

Location

Twoja Przychodnia - Centrum Medyczne Nowa Sol

Nowa Sól, 67-100, Poland

Location

Twoja Przychodnia Szczeci?skie Centrum Medyczne

Szczecin, 71-434, Poland

Location

Samodzielny Publiczny Zespo? Opieki Zdrowotnej w Tomaszow Lubelski

Tomaszów Lubelski, 22-600, Poland

Location

Klinika Reuma Park sp. z o.o. sp.k - Centrum Medyczne Reuma Park

Warsaw, 02-691, Poland

Location

MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Interventions

QL1206; Denosumab

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Clinical Development
• Organization: Fresenius Kabi SwissBioSim GmbH

medinfo_biosim@fresenius-kabi.com

+41 793075735

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2021
• First Posted: June 22, 2021
• Study Start: June 16, 2021
• Primary Completion: August 7, 2023
• Study Completion: August 7, 2023
• Last Updated: February 27, 2025
• Results First Posted: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (6); BU (12); GE (7); ES (5); HU (17); PL (29)