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

Sponsor

Fresenius Kabi SwissBioSim GmbH (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04934072

Collaborator

(none)

526

Enrollment

Locations

Arms

20.5

Anticipated Duration (Months)

6.9

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis	Drug: FKS518 Drug: US-licensed Prolia	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

526 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jul 5, 2021

Anticipated Primary Completion Date :

Mar 20, 2023

Anticipated Study Completion Date :

Mar 20, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FKS518	Drug: FKS518 Participants will receive FKS518 via subcutaneous injection, every 26 weeks.
Active Comparator: US-licensed Prolia	Drug: US-licensed Prolia Participants will receive US-licensed Prolia via subcutaneous injection, every 26 weeks.

Arm

Intervention/Treatment

Experimental: FKS518

Drug: FKS518

Participants will receive FKS518 via subcutaneous injection, every 26 weeks.

Active Comparator: US-licensed Prolia

Drug: US-licensed Prolia

Participants will receive US-licensed Prolia via subcutaneous injection, every 26 weeks.

Outcome Measures

Primary Outcome Measures

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]
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 Outcome Measures

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]
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]
Percentage Change from Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) at Week 52 [Baseline (Day 1) to Week 52]
Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) [Day 1 to Week 78]
Number of Participants Who Experience a Serious Adverse Event (SAE) [Day 1 to Week 78]
Number of Participants Who Experience a Treatment-emergent Adverse Event of Special Interest (AESI) [Day 1 to Week 78]
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.
Number of Participants Who Experience an Injection Site Reaction (ISR) [Day 1 to Week 56]
Number of Participants With Antidrug Antibodies (ADAs) [4 weeks prior to first drug administration to Week 78]
Number of Participants With Antidrug Antibody (ADA) Titers [4 weeks prior to first drug administration to Week 78]
Number of Participants With Neutralizing Antibodies (NAb) [4 weeks prior to first drug administration to Week 78]

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 85 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria

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.

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Diagnostic Consultative Center Aleksandrovska	Sofia	Sofia City	Bulgaria	1431
2	Diagnostic Consultative Center (DCC) 17 - Sofia	Sofia	Sofia City	Bulgaria	1505
3	Medical Center N. I. Pirogov	Sofia	Sofia City	Bulgaria	1612
4	Medical Center Hipokrat 2000 OOD	Haskovo		Bulgaria	6300
5	Medical Center Medconsult Pleven	Pleven		Bulgaria	5800
6	Palmed University Multidisciplinary Hospital for Active Treatment	Plovdiv		Bulgaria	4002
7	University Multi-profile Hospital for Active Treatment - Plovdiv	Plovdiv		Bulgaria	4003
8	Medical Center - Teodora EOOD	Ruse		Bulgaria	7012
9	Multiprofile Hospital for Active Treatment Hadzhi Dimitar	Sliven		Bulgaria	8800
10	Lyulin Hospital	Sofia		Bulgaria	1336
11	Diagnostic and Consultative Center Equita	Varna		Bulgaria	9002
12	Medical Center Sanador M	Vidin		Bulgaria	3703
13	CCR Brno	Brno	Jihormoravsky Kraj	Czechia	602 00
14	CCR Ostrava	Ostrava	Severomoravsky Kraj	Czechia	702 00
15	Medical Plus	Uherske Hradi?t?	South Moravian	Czechia	686 01
16	G-Centrum Olomouc s.r.o	Olomouc		Czechia	772 00
17	Artroscan	Ostrava-T?ebovice		Czechia	722 00
18	Medical Plus	Uherske Hradi?t?		Czechia	686 01
19	Center for Clinical and Basic Research AS - Tallinn	Tallinn	Harjumaa	Estonia	10128
20	Sihtasutus Pohja-Eesti Regionaalhaigla	Tallinn	Harjumaa	Estonia	13419
21	KLV Arstikabinet	Parnu	Parnumaa	Estonia	80010
22	Tartu Ulikooli Kliinikum	Tartu	Tartumaa	Estonia	50406
23	KLV Arstikabinet	Parnu		Estonia	80010
24	Evex Hospitals - Caraps Medline	Tbilisi	Borjomi	Georgia	0159
25	Georgian-Dutch Hospital	Tbilisi	Borjomi	Georgia	0172
26	Hepatology Clinic Hepa	Tbilisi		Georgia	0159
27	Tbilisi Heart And Vascular Clinic Ltd	Tbilisi		Georgia	0159
28	Jerarsi Clinic	Tbilisi		Georgia	0167
29	Raymann - Clinic of Raymann Doctors	Tbilisi		Georgia	0186
30	MedCity Ltd.	Tbilisi		Georgia	186
31	Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar	Szeged	Csongrad	Hungary	6725
32	Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz	Szentes	Csongrad	Hungary	6600
33	Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar	Szeged	Csongr	Hungary	6720
34	Szent Anna Magan N?gyogyaszati	Debrecen	Hajdu-Bihar County	Hungary	4024
35	Markhot Ferenc Oktatokorhaz es Rendel?intezet	Eger	Heves	Hungary	3300
36	Pest Megyei Flor Ferenc Korhaz	Kistarcsa	Pest	Hungary	2143
37	Obudai Egeszsegugyi Centrum	Zalaegerszeg	Zala	Hungary	8900
38	Drug Research Center Balatonfured	Balatonfured		Hungary	8230
39	Revita Rendel?	Budapest		Hungary	1027
40	Clinexpert Gyogycentrum	Budapest		Hungary	1033
41	Obudai Egeszsegugyi Centrum	Budapest		Hungary	1036
42	Semmelweis Egyetem - I. sz. Belgyogyaszati Klinika	Budapest		Hungary	1083
43	Debreceni Egyetem Klinikai Kozpont Kenezy Gyula Campus	Debrecen		Hungary	4031
44	Markhot Ferenc Oktatokorhaz es Rendel?intezet	Eger		Hungary	3300
45	Kalocsai Szent Kereszt Korhaz	Kalocsa		Hungary	6300
46	CMed Rehabilitacios es Diagnosztikai Kozpont / Saldinvest Kft.	Szekesfehervar		Hungary	8000
47	Vital Medical Center - Reumatologia	Veszprem		Hungary	8200
48	Ambulatorium Sp z o.o. - Elbl?g	Elbl?g	?u?awy	Poland	82-300
49	FutureMeds	Wroc?aw	Dolnoslaskie	Poland	50-088
50	Wromedica Centrum Zdrowia	Wroc?aw	Dolnoslaskie	Poland	51-685
51	Centrum Medyczne Oporow	Wroc?aw	Dolnoslaskie	Poland	52-416
52	Nasz Lekarz Przychodnie Medyczne	Toru?	Kujawsko-Pomorskie	Poland	87-100
53	Centrum Medyczne All-Med	Krakow	Malopolskie	Poland	30-033
54	Pratia MCM Krakow	Krakow	Malopolskie	Poland	30-510
55	RCMed Oddzial Sochaczew	Sochaczew	Mazowieckie	Poland	96-500
56	Centrum Medyczne AMED - Warszawa Targowek	Warsaw	Mazowieckie	Poland	01-518
57	Twoja Przychodnia Szczeci?skie Centrum Medyczne	Warsaw	Mazowieckie	Poland	02-777
58	Rheuma Medicus - Specjalistyczne Centrum Reumatologii i Osteoporozy	Warszawa-Ochota	Mazowieckie	Poland	02-118
59	Medycyna Kliniczna	Warszawa	Mazowieckie	Poland	00-874
60	SOMED CR - ?od?	Warszawa	Mazowieckie	Poland	04-730
61	ZDROWIE Osteo-Medic s.c. L. I A. Racewicz, A. i J. Supronik	Bia?ystok	Podlaskie	Poland	15-351
62	ClinicMed	Bia?ystok	Podlaskie	Poland	15-879
63	Nasz Lekarz O?rodek Bada? Klinicznych - Bydgoszcz	Bydgoszcz	Pomorskie	Poland	85-065
64	Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy	Bydgoszcz	Pomorskie	Poland	85-168
65	Centrum Medyczne Pratia - Gdynia	Gdynia	Pomorskie	Poland	81-338
66	Centrum Medyczne Pratia - Gdynia	Gdynia	Pomorskie	Poland	81-340
67	Gabinet diagnostyki i leczenia osteoporozy	Gliwice	Slaskie	Poland	44-122
68	Centrum Kliniczno Badawcze J Brzezicki B Gornikiewicz Brzezicka Lekarze Spo?ka Partnerska	Elbl?g	Warminsko-Mazurskie	Poland	82-300
69	Centrum Medyczne Solumed	Pozna?	Wielkopolskie	Poland	60-529
70	Centrum Bada? Klinicznych	Poznan	Wielkopolskie	Poland	60-773
71	Centrum Medyczne All-Med	Krakow		Poland	31-023
72	SOMED CR - ?od?	Lodz		Poland	90-368
73	Twoja Przychodnia - Centrum Medyczne Nowa Sol	Nowa Sol		Poland	67-100
74	Twoja Przychodnia Szczeci?skie Centrum Medyczne	Szczecin		Poland	71-434
75	Samodzielny Publiczny Zespo? Opieki Zdrowotnej w Tomaszow Lubelski	Tomaszow Lubelski		Poland	22-600
76	Klinika Reuma Park sp. z o.o. sp.k - Centrum Medyczne Reuma Park	Warszawa		Poland	02-691