A Study to Compare Efficacy, PK, PD, Safety and IMM of MB... | NCT05338086 | Trialant
NCT05338086
Sponsor
mAbxience Research S.L.
Status
Completed
Last Update Posted
Mar 21, 2025Actual
Enrollment
558Actual
Phase
Phase 3
Conditions
Postmenopausal Women With Osteoporosis
Interventions
MB09 (denosumab biosimilar)
EU-Prolia
Elemental Calcium
Vitamin D
Countries
Bulgaria
Estonia
Georgia
Hungary
Latvia
Mexico
Poland
Serbia
Protocol Section
Identification Module
NCT ID
NCT05338086
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
MB09-C-01-19
Secondary IDs
Not provided
Brief Title
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
Acronym
Not provided
Organization
mAbxience Research S.L.INDUSTRY
Status Module
Record Verification Date
Dec 2024
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Mar 16, 2022Actual
Primary Completion Date
Dec 14, 2023Actual
Completion Date
May 22, 2024Actual
First Submitted Date
Apr 8, 2022
First Submission Date that Met QC Criteria
Apr 18, 2022
First Posted Date
Apr 20, 2022Actual
Results Waived
Not provided
Results First Submitted Date
Dec 10, 2024
Results First Submitted that Met QC Criteria
Mar 17, 2025
Results First Posted Date
Mar 21, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Mar 17, 2025
Last Update Posted Date
Mar 21, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
mAbxience Research S.L.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
No
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Conditions Module
Conditions
Postmenopausal Women With Osteoporosis
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
558Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
MB09-MB09
Experimental
Subjects randomised into MB09-MB09 group were administered MB09 (60 mg in 1 mL) SC injection every 6 months.
Drug: MB09 (denosumab biosimilar)
Dietary Supplement: Elemental Calcium
Dietary Supplement: Vitamin D
Prolia-MB09
Active Comparator
Subjects randomised into Prolia- MB09 group were administered Prolia® (60 mg in 1 mL) SC injection every 6 months.
Drug: MB09 (denosumab biosimilar)
Drug: EU-Prolia
Dietary Supplement: Elemental Calcium
Dietary Supplement: Vitamin D
Prolia-Prolia
Active Comparator
Subjects randomised into Prolia-Prolia group were administered Prolia® (60 mg in 1 mL) SC injection every 6 months.
Drug: EU-Prolia
Dietary Supplement: Elemental Calcium
Dietary Supplement: Vitamin D
Interventions
Name
Type
Description
Arm Group Labels
Other Names
MB09 (denosumab biosimilar)
Drug
Pre-filled syringe (PFS) 60 mg/mL solution, administered as subcutaneous injection
MB09-MB09
Prolia-MB09
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Efficacy: Percentage Change From Baseline (%CfB) in Lumbar Spine Bone Mineral Density (LS-BMD) at 52 Weeks - Modified Full Analysis Set (mFAS)
To demonstrate equivalent efficacy of MB09 to EU Prolia in postmenopausal women with osteoporosis in terms of lumbar spine BMD at Week 52 (Month 12). The main analysis method was on the mFAS using a mixed model for repeated measures (MMRM) fitted to the composite %CfB lumbar spine BMD at Month 6 and Month 12, without any imputation of missing data. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA) and assessments of the lumbar spine (L1 to L4) were performed at a central imaging vendor.
Baseline (Screening), up to Week 52
Secondary Outcomes
Measure
Description
Time Frame
Efficacy: Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Full Analysis Set (FAS)
Difference in means (MB09-Prolia) in the %CfB in lumbar spine BMD after 12 months in postmenopausal women with osteoporosis treated with SC denosumab injections every 6 months. This included all subjects and data records irrespective of failed eligibility criteria, receipt of prohibited medications, discontinued treatment for any reason, had errors or deviations in dosing, or receipt of both doses. Estimation was via Multiple Imputation (MI) and ANCOVA on the FAS. Since the retrieved dropout rate was low, a treatment-failure (TF) penalty was applied to the imputed values at Month 12 for those subjects who received only one dose of the study treatment to centre the distribution of each subject's %CfB values around their baseline level. Bone density measurements were performed by DXA. All DXA scans were submitted to a central imaging vendor for analysis.
Other Outcomes
Not provided
Eligibility Module
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.
Supronik J, Giorgadze E, Blicharski T, Sanchez-Vidaurre S, Perez-Diaz L, Paravisini A, Millan S. Phase III Study to Confirm Clinical Similarity of MB09, a Denosumab Biosimilar, and Prolia(R) in Postmenopausal Women with Osteoporosis (SIMBA Study). Pharmaceutics. 2026 Feb 27;18(3):291. doi: 10.3390/pharmaceutics18030291.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
The study included the Screening Period (28 days before randomization) that began after the participants had signed the written informed consent form. On Day 1 of the Main Treatment Period (MTP), subjects were randomly assigned in a 2:1:1 ratio to one of the 3 arms to receive one subcutaneous (SC) injection of European Union (EU) Prolia or MB09. Only those subjects who tolerated the initial 2 doses received the third dose and proceeded to the Transition/Safety Follow-up Period (TP).
Recruitment Details
A total of 62 sites in 8 countries (Bulgaria, Estonia, Georgia, Hungary, Latvia, Poland, Serbia, and Mexico) screened at least one subject and 56 sites randomised at least one subject into the study.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
MB09 (MTP)
Subjects randomised into MB09 group received one subcutaneous (SC) injection of MB09 (60 mg/mL) every 6 months (on Day 1, and Month 6).
MB09 (denosumab biosimilar): 60 mg/mL solution for injection in Prefilled Syringe (PFS).
Daily supplementation: at least 1000 mg elemental calcium and at least 400 IU of vitamin D.
Periods
Title
Milestones
Reasons Not Completed
Main Treatment Period (Day1 to Month 12)
Type
Comment
Milestone Data
STARTED
Note: Counts are presented according to treatment as randomised except for the safety analysis set (SAF), pharmacokinetics concentration Set (PKCS), and PK parameter Set (PKPS) where counts were presented according to the treatment received. One subject was not dosed per the randomisation schedule. This was handled as an intercurrent event.
PFS 60 mg/mL solution, administered as subcutaneous injection
Prolia-MB09
Prolia-Prolia
Elemental Calcium
Dietary Supplement
at least 1000 mg daily
MB09-MB09
Prolia-MB09
Prolia-Prolia
Vitamin D
Dietary Supplement
at least 400 IU daily
MB09-MB09
Prolia-MB09
Prolia-Prolia
Baseline (screening), up to Week 52
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
To assess the efficacy of MB09 to EU-Prolia in postmenopausal women with osteoporosis in terms of Lumbar Spine at Month 6 and Total Hip and Femur Neck BMD at Month 6 and Month12. The difference in means in %CfB in lumbar spine BMD between MB09 and Prolia at Month 6 and Total Hip and Femur Neck at Month 6 and Month 12 from an MMRM presented for the mFAS. Bone density measurements were performed by DXA. All DXA scans were submitted to a central imaging vendor for analysis.
Baseline (screening), Month 6 and Month 12.
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
To assess the efficacy of MB09 to EU-Prolia in postmenopausal women with osteoporosis in terms of the difference in means (MB09-Prolia) in the %CfB in Lumbar Spine BMD at Month 6 and Total Hip and Femur Neck BMD at Month 6 and 12 in postmenopausal women with osteoporosis treated with SC denosumab injections every 6 months. This included all subjects and data records irrespective of failed eligibility criteria, receipt of prohibited medications, discontinued treatment for any reason, had errors or deviations in dosing, or receipt of both doses. Bone density measurement were performed by DXA. All DXA scans were submitted to a central imaging vendor for analysis.
Baseline (screening), Month 6, Month 12.
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)
Geometric meant (geometric CV%) sCTX Area under the effect curve from zero to 6 months (AUEC0-6 months) after first dose in postmenopausal women with osteoporosis treated with SC denosumab injections every 6 months assuming all women received their first denosumab dose without any errors in dosing and without receipt of any prohibited therapies or other osteoporosis medications up to 6 months after first dose.
Baseline (pre-dose Day 1), up to Month 6.
Pharmacodynamics: %CfB Area Under the Percent Inhibition Curve From Time Zero to 6 Months (AUIC0-6 Months) in sCTX - on mFAS
AUIC0-6 months = Area under the inhibition curve for % change from baseline sCTX concentrations from time zero to 6 months
Baseline (pre-dose Day 1), up to Month 6.
Pharmacokinetics: Maximum Observed Serum Concentration (Cmax) of Denosumab After First Dose Study Treatment (Pharmacokinetic Parameter Analysis Set)
To assess the PK profile of MB09 compared with EU-Prolia following the first dose, maximum Observed Serum Concentration (Cmax) of Denosumab After First Dose study treatment (Pharmacokinetic Parameter Analysis Set).
Baseline (pre-dose Day 1), up to Month 6
Pharmacokinetics: To Assess the PK Profile of MB09 Compared With EU Prolia (AUC0-6 Months) Following the First Dose
Area under the concentration-time curve from time zero to 6 months analysed on the log scale by ANCOVA. The model will include treatment and stratification variables (baseline BMD T-score at the lumbar spine (≤ -3.0 and > -3.0 SD), body mass index (< 25 and ≥ 25 kg/m2), age at study entry (≥ 55 to < 68 years versus ≥ 68 to ≤ 80 years) and prior bisphosphonate medication use at study entry (prior use of bisphosphonates versus no prior bisphosphonate use as fixed effects. The estimated mean difference with 95% CI will be back-transformed to give the ratio of geometric means (MB09/EU-Prolia) with 95% CI following the first dose in the Main Treatment Period.
Baseline (pre-dose Day 1), up to Month 6.
Safety: Overall Summary of Adverse Events - Main Treatment Period - Safety Analysis Set (SAF) and Safety Analysis Set for Transition Period (SAF-TP)
For Main Treatment Period, treatment-emergent adverse event (TEAE) was an event observed after first dose on Day 1 until Month 12 and no more than 6 months after the last dose in case of early treatment discontinuation unless the TEAE was considered as related to the study treatment by investigator. For Transition Period, TEAE was an event observed after the third dose of study treatment at Month 12 until Month 18. Throughout the study, TEAE was an event observed after first dose on Day 1 until Month 18.
From first administration of study treatment on Day 1 until Month 18
Safety: New Clinical Bone Fractures - TEAEs (Throughout the Study - From Day 1 Untill Month 18)
For the Main Treatment Period, TEAE was an event observed after first dose on Day 1 until Month 12 and no more than 6 months after the last dose in case of early treatment discontinuation unless the TEAE was considered as related to the study treatment by investigator. For Transition Period, TEAE was an event observed after the third dose of study treatment at Month 12 until Month 18. Throughout the study, TEAE was an event observed after first dose on Day 1 until Month 18.
All participants in the Main Treatment Period and Transition Period (From Day 1 untill Month 18)
Overall Incidence of Antidrug Antibodies (ADA) - Safety Analysis Set (SAF) and Safety Analysis Set for Transition Period (SAF-TP)
Number of subjects experiencing treatment-induced immunogenicity: Binding and neutralising serum denosumab antibodies from baseline up to and including Month 18. Analysis of immunogenicity data will be based on ADA evaluable subjects defined as all SAF or SAF-TP subjects with baseline and at least one post-baseline immunogenicity assessment within the Main Treatment Period or the Transition Period. The formation of ADAs against MB09 or EU-Prolia was assessed in blood samples.
From baseline (pre-dose) up to and including Month 18.
Pleven
Bulgaria
Medical Center Artmed OOD
Plovdiv
Bulgaria
Multiprofile Hospital for Active Treatment Plovdiv
Plovdiv
Bulgaria
Outpatient Clinic for Specialized Medical Help - Medical Center Kuchuk Paris "OOD"
Plovdiv
Bulgaria
Diagnostic and Consulting Center Aleksandrovska EOOD
Sofia
Bulgaria
Diagnostic- Consultative Center Convex EOOD
Sofia
Bulgaria
Medical Center Excelsior OOD - PPDS
Sofia
Bulgaria
Medical Center Hera EOOD
Sofia
Bulgaria
Specialized outpatient medical facility - Rheumatology Centre St. Irina EOOD
Sofia
Bulgaria
University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD
Stara Zagora
Bulgaria
New Medical Center EOOD
Vratsa
Bulgaria
Center For Clinical And Basic Research
Tallinn
Harju
Estonia
East Tallinn Central Hospital
Tallinn
Harju
Estonia
North Estonia Medical Centre Foundation
Tallinn
Harju
Estonia
KLV Arstikabinet
Pärnu
Pärnu Maakon
Estonia
Clinical Research Centre Ltd
Tartu
Tartu
Estonia
MediTrials OÜ
Tartu
Tartu
Estonia
Tartu University Hospital
Tartu
Tartu
Estonia
National Institute of Endocrinology
Tbilisi
Georgia
Tbilisi Heart and Vascular Clinic Ltd
Tbilisi
Georgia
Tbilisi Heart Center Ltd.
Tbilisi
Georgia
Bekes Megyei Kozponti Korhaz
Békéscsaba
Bekes County
Hungary
AES - DRS - Synexus Gyula - Magyarország Egészségügyi Szolgáltató Kft
Gyula
Bekes County
Hungary
Csongrad Megyei Dr. Bugyi Istvan Korhaz
Szentes
Csongrád megye
Hungary
AES - DRS - Synexus Debrecen Magyarország Egészségügyi Szolgáltató Kft
Debrecen
Hajdú-Bihar
Hungary
MÁV Kórház és Rendelointézet Szolnok
Szolnok
Jász-Nagykun-Szolnok
Hungary
Pest Megyei Flór Ferenc Kórház
Kistarcsa
Pest County
Hungary
AES - DRS - Synexus Zalaegerszeg Magyarország Egészségügyi Kft
Zalaegerszeg
Zala County
Hungary
AES - DRS - Synexus Budapest - Magyarország Egészségügyi Szolgáltató Kft
Budapest
Hungary
QUALICLINIC Kft
Budapest
Hungary
Óbudai Egészségügyi Centrum Kft
Budapest
Hungary
Vital Medical Center
Veszprém
Hungary
Private Practice of Laila Atike
Liepāja
Liepājas Rajon
Latvia
Outpatient Clinic Veselibas Centrs 4
Riga
Riga Rajon
Latvia
Outpatient Clinic Adoria
Riga
Rigas Rajons
Latvia
Sigulda Hospital, Outpatient Clinic
Sigulda
Siguldas Pilsēta
Latvia
RSU Ambulance
Riga
Latvia
Centro de Estudios de Investigacion Basica Y Clinica SC
Guadalajara
Jalisco
Mexico
Hospital Angeles Lindavista (Consultorio de Reumatologia)
Mexico City
Mexico City
Mexico
Hospital Universitario Dr. Jose Eleuterio González
Monterrey
Nuevo León
Mexico
Centro Integral Medico SJR S.C
Querétaro
Mexico
Hospital Central Dr Ignacio Morones Prieto
San Luis Potosí City
Mexico
AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Poznaniu
Poznan
Greater Poland Voivodeship
Poland
Globe Badania Kliniczne Spólka z o.o.
Kłodzko
Lower Silesian Voivodeship
Poland
Lubelskie Centrum Diagnostyczne (Lotników Polskich)
Świdnik
Lublin Voivodeship
Poland
Lubelskie Centrum Diagnostyczne
Świdnik
Lublin Voivodeship
Poland
AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Warszawie
Warsaw
Masovian Voivodeship
Poland
Bialystok - ClinicMed Daniluk, Nowak Spólka Jawna
Bialystok
Podlaskie Voivodeship
Poland
NZOZ Osteo Medic SC Artur Racewicz Jerzy Supronik
Bialystok
Podlaskie Voivodeship
Poland
Centrum Medyczne Czestochowa - PRATIA - PPDS
Częstochowa
Silesian Voivodeship
Poland
Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy
Bydgoszcz
Poland
Centrum Medyczne Katowice - PRATIA - PPDS
Katowice
Poland
Centrum Medyczne Linden
Krakow
Poland
Krakowskie Centrum Medyczne
Krakow
Poland
MCM Krakow - PRATIA - PPDS
Krakow
Poland
Centrum Medyczne AMED
Warsaw
Poland
Centrum Medyczne Reuma Park NZOZ
Warsaw
Poland
Rheuma Medicus Specjalistyczne Centrum Reumatologii i Osteoporozy
Warsaw
Poland
AES - DRS - Synexus Polska Sp. z o.o. Oddzial we Wroclawiu
Wroclaw
Poland
Institute of Rheumatology Belgrade - PPDS
Belgrade
Serbia
Military Medical Academy
Belgrade
Serbia
University Clinical Center of Serbia - PPDS
Belgrade
Serbia
Clinical Centre of Vojvodina
Novi Sad
Serbia
FG001
EU-Prolia (MTP)
Subjects randomised into Prolia-Prolia group received one SC injection of EU-Prolia® (60 mg/mL) every 6 months (on Day 1, and Month 6).
EU-Prolia®: 60 mg/mL solution for injection in PFS.
Daily supplementation: at least 1000 mg elemental calcium and at least 400 IU of vitamin D.
FG002
MB09-MB09 (TP)
Subjects randomised into MB09-MB09 group received one subcutaneous (SC) injection of MB09 (60 mg/mL) every 6 months (on Day 1, Month 6, and Month 12).
MB09 (denosumab biosimilar): 60 mg/mL solution for injection in Prefilled Syringe (PFS).
Daily supplementation: at least 1000 mg elemental calcium and at least 400 IU of vitamin D.
FG003
EU-Prolia-MB09 (TP)
Subjects randomised into Prolia-MB09 group received one SC injection of EU-Prolia® (60 mg/mL) every 6 months (on Day 1 and at Month 6) and one SC injection of MB09 at Month 12.
MB09 (denosumab biosimilar) and EU-Prolia®: 60 mg/mL solution for injection in PFS.
Daily supplementation: at least 1000 mg elemental calcium and at least 400 IU of vitamin D.
FG004
EU Prolia-EU Prolia (TP)
Subjects randomised into Prolia-Prolia group received one SC injection of EU-Prolia® (60 mg/mL) every 6 months (on Day 1, Month 6 and Month12).
EU-Prolia®: 60 mg/mL solution for injection in PFS.
Daily supplementation: at least 1000 mg elemental calcium and at least 400 IU of vitamin D.
FG000281 subjects
FG001277 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
Safety Analysis Set (SAF)
FG000277 subjects
FG001278 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
Full Analysis Set (FAS)
FG000278 subjects
FG001277 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
Modified Full Analysis Set (mFAS)
FG000258 subjects
FG001266 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
Pharmacokinetics Parameter Set (PKPS)
FG000269 subjects
FG001274 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
Pharmacokinetics Concentration Set (PKCS)
FG000277 subjects
FG001278 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
COMPLETED
Note that one subject randomly assigned to the MB09-MB09 arm did not receive the assigned treatment due to an isolated technical malfunction in the IRT system and instead received study treatment assigned to the Prolia Prolia arm throughout the study.
FG000245 subjects
FG001252 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
NOT COMPLETED
FG00036 subjects
FG00125 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
Type
Comment
Reasons
Adverse Event
FG0004 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
Lost to Follow-up
FG0001 subjects
FG0012 subjects
FG0020 subjects
FG0030 subjects
FG004
Protocol Violation
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
unrelated medical conditions
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
subject dosed in error and did not meet eligibility criteria
FG0006 subjects
FG0016 subjects
FG0020 subjects
FG0030 subjects
other
FG00023 subjects
FG00116 subjects
FG0020 subjects
FG0030 subjects
FG004
Transition Period (M12 to M18)
Type
Comment
Milestone Data
STARTED
Note: Counts were presented according to treatment as randomised except for the SAF-TP, PKCS-TP, and PKPS-TP where counts were presented according to the treatment received. One subject was not dosed per the randomisation schedule. This was handled as an intercurrent event.
FG0000 subjects
FG0010 subjects
FG002245 subjects
FG003130 subjects
FG004122 subjects
Safety Analysis Set for Transition Period (SAF-TP).
FG0000 subjects
FG0010 subjects
FG002244 subjects
FG003130 subjects
Full Analysis Set for Transition Period (FAS-TP)
FG0000 subjects
FG0010 subjects
FG002245 subjects
FG003130 subjects
Modified Full Analysis Set for Transition Period (mFAS-TP)
FG0000 subjects
FG0010 subjects
FG002233 subjects
FG003127 subjects
Pharmacokinetic Concentration Set for Transition Period (PKCS-TP)
FG0000 subjects
FG0010 subjects
FG002244 subjects
FG003130 subjects
Pharmacokinetic Parameter Set for Transition Period (PKPS-TP)
FG0000 subjects
FG0010 subjects
FG002228 subjects
FG003126 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG002239 subjects
FG003127 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0026 subjects
FG0033 subjects
FG004
Type
Comment
Reasons
Death
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG003
The Safety Analysis Set (SAF) consisted of all randomised subjects who received at least one administration of study treatment.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
MB09
•Subjects randomised into MB09 group received one subcutaneous (SC) injection of MB09 (60 mg/mL) every 6 months (on Day 1, and Month 6).
BG001
EU-Prolia
•Subjects randomised into Prolia-Prolia group received one SC injection of EU-Prolia® (60 mg/mL) every 6 months (on Day 1, and Month 6).
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000277
BG001278
BG002555
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00065.8± 6.00
BG00165.9± 5.90
BG00265.8± 5.94
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG000277
BG001278
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Race - White
Title
Measurements
BG000276
BG001275
BG002
Body Mass Index (BMI)
Mean
Standard Deviation
kg/m^2
Title
Denominators
Categories
Title
Measurements
BG00024.62± 3.01
BG00124.73± 3.06
BG002
Osteoporosis diagnosis duration
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG0002.6± 4.39
BG0012.0± 3.89
BG002
Baseline BMD T-score at the lumbar spine
The randomisation was stratified by baseline BMD T-score at the lumbar spine (≤ -3.0 and > -3.0 SD, with the worst prognosis bellow or equal to - 3 (≤ -3.0) and the better prognosis higher than -3 (> -3.0).
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
> -3.0 group
BG000144
BG001
Lumbar spine BMD
Mean
Standard Deviation
g/cm^2
Title
Denominators
Categories
Title
Measurements
BG0000.766± 0.0878
BG0010.773± 0.0862
BG002
Total hip BMD
Mean
Standard Deviation
g/cm^2
Title
Denominators
Categories
Title
Measurements
BG0000.731± 0.0973
BG0010.745± 0.0946
BG002
Femur neck BMD
Mean
Standard Deviation
g/cm^2
Title
Denominators
Categories
Title
Measurements
BG0000.672± 0.1085
BG0010.685± 0.1084
BG002
Prior use of bisphosphonates
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Yes
BG00025
BG00121
BG002
Previous Fractures in the Medical History
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Yes
BG000108
BG001102
BG002
Menopause duration
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00016.4± 7.05
BG00116.9± 7.35
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Efficacy: Percentage Change From Baseline (%CfB) in Lumbar Spine Bone Mineral Density (LS-BMD) at 52 Weeks - Modified Full Analysis Set (mFAS)
To demonstrate equivalent efficacy of MB09 to EU Prolia in postmenopausal women with osteoporosis in terms of lumbar spine BMD at Week 52 (Month 12). The main analysis method was on the mFAS using a mixed model for repeated measures (MMRM) fitted to the composite %CfB lumbar spine BMD at Month 6 and Month 12, without any imputation of missing data. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA) and assessments of the lumbar spine (L1 to L4) were performed at a central imaging vendor.
Modified Full Analysis Set (mFAS) is a subset of subjects in the FAS who met all eligibility criteria. The mFAS term defined a set at the data point level which included a data record at each timepoint for all eligible subjects in the FAS but excluded data observed after the first occurrence of those intercurrent events (ICEs) where a hypothetical strategy was taken (eg, missing a dose, errors or deviations in dosing, or receipt of any prohibited therapies or other osteoporosis medication).
Posted
Least Squares Mean
Standard Error
Percentage change (%)
Baseline (Screening), up to Week 52
ID
Title
Description
OG000
MB09
A total of 2 subcutaneous administration of 60 mg MB09 (proposed denosumab biosimilar) on Day 1 and Month 6 in the Main Treatment Period (MTP).
OG001
EU-Prolia
A total of 2 subcutaneous administration of 60 mg Prolia on Day 1 and Month 6 in the Main Treatment Period (MTP).
Units
Counts
Participants
OG000233
OG001250
Title
Denominators
Categories
Title
Measurements
OG0005.86± 0.26
OG0015.66± 0.25
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Models Analysis
MMRM included treatment, with stratification variables as classification factors and baseline BMD as a continuous covariate.
Mixed-model for repeated measures (MMRM)
Mean Difference (Final Values)
0.20
2-Sided
95
-0.51
0.91
Equivalence
The estimated mean difference in %CfB lumbar spine BMD at Month 12 was presented with 95% CI and equivalence was concluded if this fell within the predefined equivalence margin of [-1.45%, 1.45%].
Secondary
Efficacy: Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Full Analysis Set (FAS)
Difference in means (MB09-Prolia) in the %CfB in lumbar spine BMD after 12 months in postmenopausal women with osteoporosis treated with SC denosumab injections every 6 months. This included all subjects and data records irrespective of failed eligibility criteria, receipt of prohibited medications, discontinued treatment for any reason, had errors or deviations in dosing, or receipt of both doses. Estimation was via Multiple Imputation (MI) and ANCOVA on the FAS. Since the retrieved dropout rate was low, a treatment-failure (TF) penalty was applied to the imputed values at Month 12 for those subjects who received only one dose of the study treatment to centre the distribution of each subject's %CfB values around their baseline level. Bone density measurements were performed by DXA. All DXA scans were submitted to a central imaging vendor for analysis.
The Full Analysis Set (FAS) consisted of all consenting randomised subjects who received at least one dose of study treatment.
Posted
Least Squares Mean
Standard Error
Percentage change (%)
Baseline (screening), up to Week 52
ID
Title
Description
OG000
MB09
A total of 2 subcutaneous administration of 60 mg MB09 (proposed denosumab biosimilar) on Day 1 and Month 6 in the Main Treatment Period (MTP).
OG001
EU-Prolia
A total of 2 subcutaneous administration of 60 mg Prolia on Day 1 and Month 6 in the Main Treatment Period (MTP).
Secondary
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
To assess the efficacy of MB09 to EU-Prolia in postmenopausal women with osteoporosis in terms of Lumbar Spine at Month 6 and Total Hip and Femur Neck BMD at Month 6 and Month12. The difference in means in %CfB in lumbar spine BMD between MB09 and Prolia at Month 6 and Total Hip and Femur Neck at Month 6 and Month 12 from an MMRM presented for the mFAS. Bone density measurements were performed by DXA. All DXA scans were submitted to a central imaging vendor for analysis.
Modified Full Analysis Set (mFAS) is a subset of subjects in the FAS who met all eligibility criteria. The mFAS term defined a set at the data point level which included a data record at each timepoint for all eligible subjects in the FAS but excluded data observed after the first occurrence of those intercurrent events (ICEs) where a hypothetical strategy was taken (eg, missing a dose, errors or deviations in dosing, or receipt of any prohibited therapies or other osteoporosis medication).
Posted
Least Squares Mean
Standard Error
percentage change (%)
Baseline (screening), Month 6 and Month 12.
ID
Title
Description
OG000
MB09
Subcutaneous administration of 60 mg MB09 (proposed denosumab biosimilar) every 6 months, on Day 1 and Month 6 in the Main Treatment Period (MTP).
OG001
EU-Prolia
Subcutaneous administration of 60 mg Prolia every 6 months, on Day 1 and Month 6 in the Main Treatment Period (MTP).
Secondary
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
To assess the efficacy of MB09 to EU-Prolia in postmenopausal women with osteoporosis in terms of the difference in means (MB09-Prolia) in the %CfB in Lumbar Spine BMD at Month 6 and Total Hip and Femur Neck BMD at Month 6 and 12 in postmenopausal women with osteoporosis treated with SC denosumab injections every 6 months. This included all subjects and data records irrespective of failed eligibility criteria, receipt of prohibited medications, discontinued treatment for any reason, had errors or deviations in dosing, or receipt of both doses. Bone density measurement were performed by DXA. All DXA scans were submitted to a central imaging vendor for analysis.
The Full Analysis Set (FAS) consisted of all consenting randomised subjects who received at least one dose of study treatment.
Posted
Least Squares Mean
Standard Error
percentage change (%)
Baseline (screening), Month 6, Month 12.
ID
Title
Description
OG000
MB09
A total of 2 subcutaneous administration of 60 mg MB09 (proposed denosumab biosimilar) on Day 1 and Month 6 in the Main Treatment Period (MTP).
OG001
EU-Prolia
A total of 2 subcutaneous administration of 60 mg Prolia on Day 1 and Month 6 in the Main Treatment Period (MTP).
Secondary
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)
Geometric meant (geometric CV%) sCTX Area under the effect curve from zero to 6 months (AUEC0-6 months) after first dose in postmenopausal women with osteoporosis treated with SC denosumab injections every 6 months assuming all women received their first denosumab dose without any errors in dosing and without receipt of any prohibited therapies or other osteoporosis medications up to 6 months after first dose.
Modified Full Analysis Set (mFAS)
Posted
Geometric Mean
Geometric Coefficient of Variation
day*pg/mL
Baseline (pre-dose Day 1), up to Month 6.
ID
Title
Description
OG000
MB09
Subcutaneous administration of 60 mg MB09 (proposed denosumab biosimilar) every 6 months, on Day 1 and Month 6 in the Main Treatment Period (MTP).
OG001
EU-Prolia
Subcutaneous administration of 60 mg Prolia every 6 months, on Day 1 and Month 6 in the Main Treatment Period (MTP).
Units
Counts
Participants
Secondary
Pharmacodynamics: %CfB Area Under the Percent Inhibition Curve From Time Zero to 6 Months (AUIC0-6 Months) in sCTX - on mFAS
AUIC0-6 months = Area under the inhibition curve for % change from baseline sCTX concentrations from time zero to 6 months
Modified Full Analysis Set (mFAS)
Posted
Geometric Mean
Geometric Coefficient of Variation
day* %
Baseline (pre-dose Day 1), up to Month 6.
ID
Title
Description
OG000
MB09
Subcutaneous administration of 60 mg MB09 (proposed denosumab biosimilar) every 6 months, on Day 1 and Month 6 in the Main Treatment Period (MTP).
OG001
EU-Prolia
Subcutaneous administration of 60 mg Prolia every 6 months, on Day 1 and Month 6 in the Main Treatment Period (MTP).
Units
Counts
Participants
OG000
Secondary
Pharmacokinetics: Maximum Observed Serum Concentration (Cmax) of Denosumab After First Dose Study Treatment (Pharmacokinetic Parameter Analysis Set)
To assess the PK profile of MB09 compared with EU-Prolia following the first dose, maximum Observed Serum Concentration (Cmax) of Denosumab After First Dose study treatment (Pharmacokinetic Parameter Analysis Set).
Pharmacokinetic Parameter Analysis Set (PKPS) comprises all subjects who have at least three measurable concentrations in PKCS which must include Day 11 to allow for reliable estimation of both Cmax and AUC0-6 months.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Baseline (pre-dose Day 1), up to Month 6
ID
Title
Description
OG000
MB09
Subcutaneous administration of 60 mg MB09 (proposed denosumab biosimilar) every 6 months, on Day 1 and Month 6 in the Main Treatment Period (MTP).
OG001
EU-Prolia
Subcutaneous administration of 60 mg Prolia every 6 months, on Day 1 and Month 6 in the Main Treatment Period (MTP).
Units
Counts
Participants
Secondary
Pharmacokinetics: To Assess the PK Profile of MB09 Compared With EU Prolia (AUC0-6 Months) Following the First Dose
Area under the concentration-time curve from time zero to 6 months analysed on the log scale by ANCOVA. The model will include treatment and stratification variables (baseline BMD T-score at the lumbar spine (≤ -3.0 and > -3.0 SD), body mass index (< 25 and ≥ 25 kg/m2), age at study entry (≥ 55 to < 68 years versus ≥ 68 to ≤ 80 years) and prior bisphosphonate medication use at study entry (prior use of bisphosphonates versus no prior bisphosphonate use as fixed effects. The estimated mean difference with 95% CI will be back-transformed to give the ratio of geometric means (MB09/EU-Prolia) with 95% CI following the first dose in the Main Treatment Period.
Pharmacokinetic Parameter Analysis Set (PKPS) comprises all subjects who have at least three measurable concentrations in PKCS wich must include Day 11 to allow for reliable estimation of both Cmax and AUC0-6 months.
Posted
Geometric Mean
Geometric Coefficient of Variation
day*ng/mL
Baseline (pre-dose Day 1), up to Month 6.
ID
Title
Description
OG000
MB09
Subcutaneous administration of 60 mg MB09 (proposed denosumab biosimilar) every 6 months, on Day 1 and Month 6 in the Main Treatment Period (MTP).
OG001
EU-Prolia
Subcutaneous administration of 60 mg Prolia every 6 months, on Day 1 and Month 6 in the Main Treatment Period (MTP).
Secondary
Safety: Overall Summary of Adverse Events - Main Treatment Period - Safety Analysis Set (SAF) and Safety Analysis Set for Transition Period (SAF-TP)
For Main Treatment Period, treatment-emergent adverse event (TEAE) was an event observed after first dose on Day 1 until Month 12 and no more than 6 months after the last dose in case of early treatment discontinuation unless the TEAE was considered as related to the study treatment by investigator. For Transition Period, TEAE was an event observed after the third dose of study treatment at Month 12 until Month 18. Throughout the study, TEAE was an event observed after first dose on Day 1 until Month 18.
The Safety Analysis Set (SAF) and Safety Analysis Set for Transition Period (SAF-TP)
Posted
Count of Participants
Participants
From first administration of study treatment on Day 1 until Month 18
ID
Title
Description
OG000
Main Treatment Period: MB09
From first administration of study treatment on Day 1 until Month 12 (pre-dose) displayed for MB09 group.
OG001
Main Treatment Period: EU-Prolia
From first administration of study treatment on Day 1 until Month 12 (pre-dose) displayed for EU-Prolia group.
OG002
Throughout the Study: MB09-MB09
Secondary
Safety: New Clinical Bone Fractures - TEAEs (Throughout the Study - From Day 1 Untill Month 18)
For the Main Treatment Period, TEAE was an event observed after first dose on Day 1 until Month 12 and no more than 6 months after the last dose in case of early treatment discontinuation unless the TEAE was considered as related to the study treatment by investigator. For Transition Period, TEAE was an event observed after the third dose of study treatment at Month 12 until Month 18. Throughout the study, TEAE was an event observed after first dose on Day 1 until Month 18.
Safety Analysis Set (SAF) and Safety Analysis Set for Transition Period (SAF-TP)
Posted
Count of Participants
Participants
All participants in the Main Treatment Period and Transition Period (From Day 1 untill Month 18)
ID
Title
Description
OG000
Throughout the Study: MB09-MB09
Cumulative safety data throughout the study (baseline to the end of Transition Period [Month 18]) displayed for MB09-MB09 group.
OG001
Throughout the Study: EU Prolia-MB09
Cumulative safety data throughout the study (baseline to the end of Transition Period [Month 18]) displayed for EU Prolia-MB09 group.
OG002
Throughout the Study: EU Prolia- EU Prolia
Secondary
Overall Incidence of Antidrug Antibodies (ADA) - Safety Analysis Set (SAF) and Safety Analysis Set for Transition Period (SAF-TP)
Number of subjects experiencing treatment-induced immunogenicity: Binding and neutralising serum denosumab antibodies from baseline up to and including Month 18. Analysis of immunogenicity data will be based on ADA evaluable subjects defined as all SAF or SAF-TP subjects with baseline and at least one post-baseline immunogenicity assessment within the Main Treatment Period or the Transition Period. The formation of ADAs against MB09 or EU-Prolia was assessed in blood samples.
Safety Analysis Set (SAF) and Safety Analysis Set for Transition Period (SAF-TP)
Posted
Count of Participants
Participants
From baseline (pre-dose) up to and including Month 18.
ID
Title
Description
OG000
Throughout the Study: MB09-MB09
Cumulative safety data throughout the study (baseline to the end of Transition Period [Month 18]) displayed for MB09-MB09 group.
OG001
Throughout the Study: EU Prolia-MB09
Cumulative safety data throughout the study (baseline to the end of Transition Period [Month 18]) displayed for EU Prolia-MB09 group.
OG002
Throughout the Study: EU Prolia- EU Prolia
Time Frame
Subject incidence of TEAEs up to and including Month 18.
Description
For Main Treatment Period, TEAE was an event observed after first dose on Day 1 until Month 12 and no more than 6 months after the last dose in case of early treatment discontinuation unless the TEAE was considered as related to the study treatment by investigator. For Transition Period, TEAE was an event observed after the third dose of study treatment at Month 12 until Month 18. Throughout the study, TEAE was an event observed after first dose on Day 1 until Month 18.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Main Treatment Period: MB09
From first administration of study treatment on Day 1 until Month 12 (pre-dose) displayed for MB09 group.
0
277
19
277
120
277
EG001
Main Treatment Period: EU-Prolia
From first administration of study treatment on Day 1 until Month 12 (pre-dose) displayed for EU-Prolia group.
0
278
13
278
120
278
EG002
Throughout the Study: MB09-MB09
Cumulative safety data throughout the study (baseline to the end of Transition Period [Month 18]) displayed for MB09-MB09 group.
1
277
21
277
180
277
EG003
Throughout the Study: EU Prolia-MB09
Cumulative safety data throughout the study (baseline to the end of Transition Period [Month 18]) displayed for EU Prolia-MB09 group.
0
140
11
140
87
140
EG004
Throughout the Study: EU Prolia-EU Prolia
Cumulative safety data throughout the study (baseline to the end of Transition Period [Month 18]) displayed for EU Prolia-EU Prolia group.
0
138
4
138
75
138
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Angina pectoris
Cardiac disorders
MedDRA, Version 24.1
Systematic Assessment
EG0000 events0 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG0030 events0 affected140 at risk
EG0040 events0 affected138 at risk
Angina unstable
Cardiac disorders
MedDRA, Version 24.1
Systematic Assessment
EG0000 events0 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA, Version 24.1
Systematic Assessment
EG0001 events1 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Supraventricular tachycardia
Cardiac disorders
MedDRA, Version 24.1
Systematic Assessment
EG0001 events1 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Bundle branch block left
Cardiac disorders
MedDRA, Version 24.1
Systematic Assessment
EG0000 events0 affected277 at risk
EG0011 events1 affected278 at risk
EG0020 events0 affected277 at risk
EG003
Cardiac disorder
Cardiac disorders
MedDRA, Version 24.1
Systematic Assessment
EG0000 events0 affected277 at risk
EG0010 events0 affected278 at risk
EG0020 events0 affected277 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA, Version 24.1
Systematic Assessment
EG0001 events1 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Ileus paralytic
Gastrointestinal disorders
MedDRA, Version 24.1
Systematic Assessment
EG0001 events1 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Large intestine polyp
Gastrointestinal disorders
MedDRA, Version 24.1
Systematic Assessment
EG0001 events1 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Gastric polyps
Gastrointestinal disorders
MedDRA, Version 24.1
Systematic Assessment
EG0000 events0 affected277 at risk
EG0011 events1 affected278 at risk
EG0020 events0 affected277 at risk
EG003
Pancreatitis acute
Gastrointestinal disorders
MedDRA, Version 24.1
Systematic Assessment
EG0000 events0 affected277 at risk
EG0011 events1 affected278 at risk
EG0020 events0 affected277 at risk
EG003
Pneumonia
Infections and infestations
MedDRA, Version 24.1
Systematic Assessment
EG0001 events1 affected277 at risk
EG0010 events0 affected278 at risk
EG0022 events2 affected277 at risk
EG003
Pneumonia haemophilus
Infections and infestations
MedDRA, Version 24.1
Systematic Assessment
EG0000 events0 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Pulmonary tuberculosis
Infections and infestations
MedDRA, Version 24.1
Systematic Assessment
EG0001 events1 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA, Version 24.1
Systematic Assessment
EG0000 events0 affected277 at risk
EG0010 events0 affected278 at risk
EG0020 events0 affected277 at risk
EG003
Post-acute COVID-19 syndrome
Infections and infestations
MedDRA, Version 24.1
Systematic Assessment
EG0000 events0 affected277 at risk
EG0011 events1 affected278 at risk
EG0020 events0 affected277 at risk
EG003
Hip fracture
Musculoskeletal and connective tissue disorders
MedDRA, Version 24.1
Systematic Assessment
EG0001 events1 affected277 at risk
EG0011 events1 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Osteonecrosis of jaw
Musculoskeletal and connective tissue disorders
MedDRA, Version 24.1
Systematic Assessment
EG0001 events1 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Ulna fracture
Musculoskeletal and connective tissue disorders
MedDRA, Version 24.1
Systematic Assessment
EG0001 events1 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Ankle fracture
Musculoskeletal and connective tissue disorders
MedDRA, Version 24.1
Systematic Assessment
EG0000 events0 affected277 at risk
EG0011 events1 affected278 at risk
EG0020 events0 affected277 at risk
EG003
Intervertebral disc disorder
Musculoskeletal and connective tissue disorders
MedDRA, Version 24.1
Systematic Assessment
EG0000 events0 affected277 at risk
EG0011 events1 affected278 at risk
EG0020 events0 affected277 at risk
EG003
Spinal osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA, Version 24.1
Systematic Assessment
EG0000 events0 affected277 at risk
EG0011 events1 affected278 at risk
EG0020 events0 affected277 at risk
EG003
Adenocarcinoma metastatic
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA, Version 24.1
Systematic Assessment
EG0001 events1 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Pituitary tumour benign
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA, Version 24.1
Systematic Assessment
EG0001 events1 affected277 at risk
EG0010 events0 affected278 at risk
EG0021 events1 affected277 at risk
EG003
Renal cancer metastatic
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ANCOVA included terms for treatment, with stratification variables as classification factors and baseline BMD included as a continuous covariate.
Mean Difference (Final Values)
0.03
2-Sided
95
-0.69
0.74
The estimated mean difference in %CfB lumbar spine BMD results was pooled using Rubin's methods and presented with 95% CI.
Equivalence
The estimated mean difference in %CfB lumbar spine BMD at Month 12 was presented with 95% CI and equivalence was concluded if this fell within the predefined equivalence margin of [-1.45%, 1.45%].
Units
Counts
Participants
OG000258
OG001266
Title
Denominators
Categories
Total Hip - Month 12
ParticipantsOG000232
ParticipantsOG001252
Title
Measurements
OG0003.37± 0.18
OG0013.28± 0.17
Femur Neck - Month 12
ParticipantsOG000232
ParticipantsOG001252
Title
Measurements
OG0002.75± 0.23
OG001
Lumbar Spine - Month 6
ParticipantsOG000246
ParticipantsOG001258
Title
Measurements
OG0004.03± 0.23
OG001
Total Hip - Month 6
ParticipantsOG000241
ParticipantsOG001257
Title
Measurements
OG0002.29± 0.16
OG001
Femur Neck - Month 6
ParticipantsOG000241
ParticipantsOG001257
Title
Measurements
OG0002.18± 0.22
OG001
Units
Counts
Participants
OG000278
OG001277
Title
Denominators
Categories
Total Hip - Month 12
ParticipantsOG000254
ParticipantsOG001260
Title
Measurements
OG0003.31± 0.17
OG0013.27± 0.17
Femur Neck- Month 12
ParticipantsOG000254
ParticipantsOG001260
Title
Measurements
OG0002.70± 0.23
OG001
Lumbar Spine - Month 6
ParticipantsOG000278
ParticipantsOG001277
Title
Measurements
OG0003.82± 0.22
OG001
Total Hip - Month 6
ParticipantsOG000262
ParticipantsOG001270
Title
Measurements
OG0002.28± 0.16
OG001
Femur Neck - Month 6
ParticipantsOG000262
ParticipantsOG001270
Title
Measurements
OG0002.18± 0.21
OG001
OG000218
OG001228
Title
Denominators
Categories
Title
Measurements
OG00012300± 49.7
OG00112400± 44.1
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
ANCOVA model including log-transformed baseline sCTX as a continuous covariate with treatment and stratification variables as fixed effects.
Ratio of Geometric means
99.91
2-Sided
95
91.99
108.52
Equivalence
Equivalence criteria (analysis set mFAS): 95% CI for ratio of geometric LS mean ratios contained in acceptance limits (80.00%, 125.00%).
218
OG001228
Title
Denominators
Categories
Title
Measurements
OG00015100± 17.4
OG00115300± 13.6
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
Ratio of Geometric means
99.13
2-Sided
95
96.31
102.02
Equivalence
Biosimilarity with respect to PD was concluded if the 95% CI for the test (MB09) to reference (EU-Prolia) ratios of the geometric LS means was contained within the [80.00%, 125.00%] interval.
OG000269
OG001273
Title
Denominators
Categories
Title
Measurements
OG0005960± 31.1
OG0015700± 35.9
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
Cmax was analysed on the log scale by ANCOVA. The model included treatment and stratification variables as fixed effects.
LS Geometric Mean Ratio
104.13
2-Sided
95
98.83
109.71
Equivalence
Equivalence criteria (on Pharmacokinetic Parameter Analysis Set): the 95% CIs around the geometric LS mean contained in the acceptance limits (80.00%, 125.00%)
Units
Counts
Participants
OG000256
OG001260
Title
Denominators
Categories
Title
Measurements
OG000360,000± 36.5
OG001337000± 39.5
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
AUC0-6 months was analysed on the log scale by ANCOVA. The model included treatment and stratification variables as fixed effects.
LS Geometric Mean Ratio
106.06
2-Sided
95
99.84
112.66
Equivalence
Equivalence criteria (on Pharmacokinetic Parameter Analysis Set): the 95% CIs around the geometric LS mean contained in the acceptance limits (80.00%, 125.00%)
Cumulative safety data throughout the study (baseline to the end of Transition Period [Month 18]) displayed for MB09-MB09 group.
OG003
Throughout the Study: Prolia-MB09
Cumulative safety data throughout the study (baseline to the end of Transition Period [Month 18]) displayed for Prolia-MB09 group.
OG004
Throughout the Study: Prolia-Prolia
Cumulative safety data throughout the study (baseline to the end of Transition Period [Month 18]) displayed for Prolia-Prolia group.
Units
Counts
Participants
OG000277
OG001278
OG002277
OG003140
OG004138
Title
Denominators
Categories
Any TEAEs
Title
Measurements
OG000161
OG001150
OG002180
OG00387
OG00475
Any study treatment-related TEAEs
Title
Measurements
OG00041
OG00124
OG00245
OG003
Any serious TEAEs
Title
Measurements
OG00019
OG00113
OG00221
OG003
Any study treatment-related serious TEAEs
Title
Measurements
OG0001
OG0011
OG0021
OG003
Cumulative safety data throughout the study (baseline to the end of Transition Period [Month 18]) displayed for EU Prolia- EU Prolia group.
Units
Counts
Participants
OG000277
OG001140
OG002138
Title
Denominators
Categories
Number of subjects with at least one fracture TEAE (any bone)
Title
Measurements
OG00012
OG0016
OG0024
Number of subjects with at least one Vertebral fracture
Title
Measurements
OG0003
OG0012
OG0021
Number of subjects with at least one Hip fracture
Title
Measurements
OG0001
OG0011
OG0020
Number of subjects with at least one Pelvic fracture
Title
Measurements
OG0001
OG0010
OG0020
Cumulative safety data throughout the study (baseline to the end of Transition Period [Month 18]) displayed for EU Prolia- EU Prolia group.