Clinical trial NCT05338086: A Study to Compare Efficacy, PK, PD, Safety and IMM of MB09 to Prolia® [EU-sourced] in Postmenopausal Osteoporosis.
Official title: A Randomised, Double-blind, Parallel, Multinational Study to Compare the Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of MB09 (Proposed Denosumab Biosimilar) vs. Prolia® (EU-sourced) in Postmenopausal Osteoporosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postmenopausal Women With Osteoporosis
Lead sponsor: mAbxience Research S.L.
Sponsor class: INDUSTRY
First posted: 2022-04-20
Enrollment: 558
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a randomized, double-blind, parallel, multicenter, multinational study to compare the efficacy, pharmacokinetics, pharmacodynamics, safety and immunogenicity of MB09 versus Prolia® in postmenopausal women with osteoporosis

Detailed description: The study was planning to randomise approximately 528 postmenopausal women with osteoporosis aged ≥55 and ≤80 years old with a Bone Mineral Density (BMD) consistent with T-score of ≤ -2.5 and ≥ -4 at the lumbar spine or total hip as measured by DXA during the Screening Period. Screening evaluations were to be completed within 28 days prior to randomisation.

On Day 1, 528 eligible postmenopausal women with osteoporosis were to be randomised in a 2:1:1 ratio to receive MB09-MB09 (Arm 1), Prolia-MB09 (Arm 2), or Prolia-Prolia (Arm 3) using an Interactive Response Sys-tem (IRT).

During the Main Treatment Period, subjects received one subcutaneous injection (60 mg/mL) of study drug on Day 1 and at Month 6. At Month 12, after all efficacy and safety assessments have been performed, the subject were to be enter the Transition/Safety Follow Up Period and were to receive the third dose of study drug. Subjects assigned to the MB09 MB09 arm (Arm 1) received MB09 on Day 1, at Month 6 and at Month 12. Subjects assigned to the Prolia MB09 arm (Arm 2) received EU-Prolia on Day 1 and at Month 6, and MB09 at Month 12. Subjects assigned to the Prolia-Prolia arm (Arm 3) received EU-Prolia on Day 1, at Month 6, and at Month 12. All subjects were to be followed up to Transition Period Month 6.

All subjects received daily supplementation of calcium and vitamin D.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal women, diagnosed with osteoporosis.
* Aged ≥ 55 and ≤ 80 years at screening.
* Body weight ≥ 50 kg and ≤ 99.9 kg, and a body mass index of ≤30 kg/m2 at screening.
* Absolute bone mineral density consistent with T-score ≤ -2.5 and ≥ -4.0 at the lumbar spine or total hip as measured by Dual-energy X-ray Absorptiometry (DXA).
* At least two intact, nonfractured vertebrae in the L1-L4 region and at least one hip joint evaluable by DXA.
* Adequate organ function.

Exclusion Criteria:

* Previous exposure to denosumab (Prolia®, Xgeva®, or denosumab biosimilar) or other monoclonal antibody.
* History and/or presence of one severe or more than two moderate vertebral fractures or hip fracture.
* Recent long bone fracture (within 6 months).
* History and/or presence of bone metastases, bone disease or other metabolic disease.
* Intravenous bisphosphonate administered within 5 years of screening.
* Oral bisphosphonates ≥12 months cumulative use prior to screening. If used \<12 months cumulatively and the last dose was ≥12 months before screening, the subject could be enrolled.
* Ongoing use of any osteoporosis treatment or use of prohibited treatment.
* Other bone active drugs.
* History and/or current hypoparathyroidism or hyperparathyroidism, hypocalcemia or hypercalcemia.
* Other Inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Efficacy: Percentage Change From Baseline (%CfB) in Lumbar Spine Bone Mineral Density (LS-BMD) at 52 Weeks - Modified Full Analysis Set (mFAS)
timeFrame: Baseline (Screening), up to Week 52
Secondary outcomes:
measure: Efficacy: Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Full Analysis Set (FAS)
timeFrame: Baseline (screening), up to Week 52
measure: Efficacy: Percentage Change From Baseline (%CfB) in Lumbar Spine at Month 6 and Total Hip and Femur Neck BMD at Month 6 and Month12 - MMRM on mFAS
timeFrame: Baseline (screening), Month 6 and Month 12.
measure: Efficacy: Percentage Change From Baseline (%CfB) in Lumbar Spine BMD at Month 6 and Total Hip and Femur Neck BMD at Month 6 and 12 - ANCOVA on FAS
timeFrame: Baseline (screening), Month 6, Month 12.
measure: Pharmacodynamics: Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (sCTX) Area Under the Effect Curve From Zero to 6 Months (AUEC0-6 Months) After First Dose - Modified Full Analysis Set (mFAS)
timeFrame: Baseline (pre-dose Day 1), up to Month 6.
measure: Pharmacodynamics: %CfB Area Under the Percent Inhibition Curve From Time Zero to 6 Months (AUIC0-6 Months) in sCTX - on mFAS
timeFrame: Baseline (pre-dose Day 1), up to Month 6.
measure: Pharmacokinetics: Maximum Observed Serum Concentration (Cmax) of Denosumab After First Dose Study Treatment (Pharmacokinetic Parameter Analysis Set)
timeFrame: Baseline (pre-dose Day 1), up to Month 6
measure: Pharmacokinetics: To Assess the PK Profile of MB09 Compared With EU Prolia (AUC0-6 Months) Following the First Dose
timeFrame: Baseline (pre-dose Day 1), up to Month 6.
measure: Safety: Overall Summary of Adverse Events - Main Treatment Period - Safety Analysis Set (SAF) and Safety Analysis Set for Transition Period (SAF-TP)
timeFrame: From first administration of study treatment on Day 1 until Month 18
measure: Safety: New Clinical Bone Fractures - TEAEs (Throughout the Study - From Day 1 Untill Month 18)
timeFrame: All participants in the Main Treatment Period and Transition Period (From Day 1 untill Month 18)
measure: Overall Incidence of Antidrug Antibodies (ADA) - Safety Analysis Set (SAF) and Safety Analysis Set for Transition Period (SAF-TP)
timeFrame: From baseline (pre-dose) up to and including Month 18.
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: AES - DRS - Medical Center Synexus Sofia EOOD
state: Sofia-Grad
city: Pleven
country: Bulgaria
facility: Medical Center Medconsult Pleven OOD
city: Plovdiv
country: Bulgaria
facility: Medical Center Artmed OOD
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Plovdiv
city: Plovdiv
country: Bulgaria
facility: Outpatient Clinic for Specialized Medical Help - Medical Center Kuchuk Paris "OOD"
city: Sofia
country: Bulgaria
facility: Diagnostic and Consulting Center Aleksandrovska EOOD
city: Sofia
country: Bulgaria
facility: Diagnostic- Consultative Center Convex EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Excelsior OOD - PPDS
city: Sofia
country: Bulgaria
facility: Medical Center Hera EOOD
city: Sofia
country: Bulgaria
facility: Specialized outpatient medical facility - Rheumatology Centre St. Irina EOOD
city: Stara Zagora
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD
city: Vratsa
country: Bulgaria
facility: New Medical Center EOOD
city: Tallinn
country: Estonia
facility: Center For Clinical And Basic Research
state: Harjumaa
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
state: Harjumaa
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation
state: Harjumaa
city: Pärnu
country: Estonia
facility: KLV Arstikabinet
state: Pärnu Maakon
city: Tartu
country: Estonia
facility: Clinical Research Centre Ltd
state: Tartumaa
city: Tartu
country: Estonia
facility: MediTrials OÜ
state: Tartumaa
city: Tartu
country: Estonia
facility: Tartu University Hospital
state: Tartumaa
city: Tbilisi
country: Georgia
facility: National Institute of Endocrinology
city: Tbilisi
country: Georgia
facility: Tbilisi Heart and Vascular Clinic Ltd
city: Tbilisi
country: Georgia
facility: Tbilisi Heart Center Ltd.
city: Békéscsaba
country: Hungary
facility: Bekes Megyei Kozponti Korhaz
state: Békés
city: Gyula
country: Hungary
facility: AES - DRS - Synexus Gyula - Magyarország Egészségügyi Szolgáltató Kft
state: Békés
city: Szentes
country: Hungary
facility: Csongrad Megyei Dr. Bugyi Istvan Korhaz
state: Csongrád
city: Debrecen
country: Hungary
facility: AES - DRS - Synexus Debrecen Magyarország Egészségügyi Szolgáltató Kft
state: Hajdú-Bihar
city: Szolnok
country: Hungary
facility: MÁV Kórház és Rendelointézet Szolnok
state: Jász-Nagykun-Szolnok
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flór Ferenc Kórház
state: Pest
city: Zalaegerszeg
country: Hungary
facility: AES - DRS - Synexus Zalaegerszeg Magyarország Egészségügyi Kft
state: Zala
city: Budapest
country: Hungary
facility: AES - DRS - Synexus Budapest - Magyarország Egészségügyi Szolgáltató Kft
city: Budapest
country: Hungary
facility: QUALICLINIC Kft
city: Budapest
country: Hungary
facility: Óbudai Egészségügyi Centrum Kft
city: Veszprém
country: Hungary
facility: Vital Medical Center
city: Liepāja
country: Latvia
facility: Private Practice of Laila Atike
state: Liepājas Rajon
city: Riga
country: Latvia
facility: Outpatient Clinic Veselibas Centrs 4
state: Riga Rajon
city: Riga
country: Latvia
facility: Outpatient Clinic Adoria
state: Rigas Rajons
city: Sigulda
country: Latvia
facility: Sigulda Hospital, Outpatient Clinic
state: Siguldas Pilsēta
city: Riga
country: Latvia
facility: RSU Ambulance
city: Ciudad de Mexico
country: Mexico
facility: Hospital Angeles Lindavista (Consultorio de Reumatologia)
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Centro de Estudios de Investigacion Basica Y Clinica SC
state: Jalisco
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio González
state: Nuevo León
city: Querétaro
country: Mexico
facility: Centro Integral Medico SJR S.C
city: San Luis Potosí
country: Mexico
facility: Hospital Central Dr Ignacio Morones Prieto
city: Kłodzko
country: Poland
facility: Globe Badania Kliniczne Spólka z o.o.
state: Dolnoslaskie
city: Świdnik
country: Poland
facility: Lubelskie Centrum Diagnostyczne (Lotników Polskich)
state: Lubelskie
city: Świdnik
country: Poland
facility: Lubelskie Centrum Diagnostyczne
state: Lubelskie
city: Warszawa
country: Poland
facility: AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Warszawie
state: Mazowieckie
city: Bialystok
country: Poland
facility: Bialystok - ClinicMed Daniluk, Nowak Spólka Jawna
state: Podlaskie
city: Bialystok
country: Poland
facility: NZOZ Osteo Medic SC Artur Racewicz Jerzy Supronik
state: Podlaskie
city: Częstochowa
country: Poland
facility: Centrum Medyczne Czestochowa - PRATIA - PPDS
state: Slaskie
city: Poznań
country: Poland
facility: AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Poznaniu
state: Wielkopolskie
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy
city: Katowice
country: Poland
facility: Centrum Medyczne Katowice - PRATIA - PPDS
city: Krakow
country: Poland
facility: Krakowskie Centrum Medyczne
city: Kraków
country: Poland
facility: Centrum Medyczne Linden
city: Kraków
country: Poland
facility: MCM Krakow - PRATIA - PPDS
city: Warsaw
country: Poland
facility: Centrum Medyczne AMED
city: Warsaw
country: Poland
facility: Centrum Medyczne Reuma Park NZOZ
city: Warsaw
country: Poland
facility: Rheuma Medicus Specjalistyczne Centrum Reumatologii i Osteoporozy
city: Wrocław
country: Poland
facility: AES - DRS - Synexus Polska Sp. z o.o. Oddzial we Wroclawiu
city: Belgrad
country: Serbia
facility: Institute of Rheumatology Belgrade - PPDS
city: Belgrad
country: Serbia
facility: Military Medical Academy
city: Belgrad
country: Serbia
facility: University Clinical Center of Serbia - PPDS
city: Novi Sad
country: Serbia
facility: Clinical Centre of Vojvodina
Study officials:
References: