Postmenopausal women diagnosed with osteoporosis MedDRA version: 20.0 Level: PT Classification code 10031285 Term: Osteoporosis postmenopausal System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: MB09
Product Code: MB09
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Denosumab
CAS Number: 615258-40-7
Current Sponsor code: MB09
Concentration
Sponsors
mAbxience Research S.L.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Signed informed consent must be obtained prior to participation in the study. 2.Postmenopausal women. Postmenopausal status is defined as at least 12 consecutive months of amenorrhea prior to date of screening with a follicle-stimulating hormone level of =30 mIU/mL or surgical menopause (bilateral oophorectomy with or without hysterectomy) =12 months prior to the screening visit when follicle-stimulating hormone is not required. 3.Aged =55 and =80 years at screening. 4.Body weight =50 kg and =99.9 kg, and a body mass index of =30 kg/m2 at screening. 5.Absolute BMD consistent with T-score =-2.5 and =-4 at the lumbar spine or total hip as measured by DXA during the Screening Period. 6.At least two intact, nonfractured vertebrae in the L1 to L4 region (vertebrae to be assessed by central reading of lateral spine X-ray during the Screening Period) and at least one hip joint are evaluable by DXA. 7.Adequate organ function as defined by the following criteria: •Normal levels of vitamin D (=20 to =64 ng/mL) and calcium (=8.5 to =10.5 mg/dL) at screening. •Serum aspartate aminotransferase, alanine aminotransferase and bilirubin =2.0 × ULN in the absence of any evidence of viral hepatitis. •Platelets =100 × 109/L. •Haemoglobin =9.0 g/dL. •Albumin 3.4 to 5.4 g/dL. •Glomerular filtration rate >30 mL/min. •Adequate coagulation parameters such as: INR =2.0 and aPTT =1.5 × ULN. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 264 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 264
Exclusion criteria
Exclusion criteria: 1.Previous exposure to denosumab or any other monoclonal antibody or fusion protein containing IgG or other biologic agent targeting IgG 2.Confirmed or suspected with SARS-CoV-2 at screening or has been diagnosed with COVID-19 or had contact with a COVID-19 infected patient within 14 days of screening 3.Height, weight or girth that may preclude accurate DXA measurements 4. History and/or presence of one severe or more than two moderate vertebral fractures or hip fracture 5.Recent long bone fracture (within 6 months). Presence of active healing fracture according to assessment of investigators 6.History and/or presence of bone metastases, bone disease, or metabolic disease other than osteoporosis, which could interfere with the interpretation of the findings 7.Malignancy within the 5 years before enrolment (except cervical carcinoma in situ or basal cell carcinoma, which are not prohibitive) 8.Drugs being investigated for osteoporosis 9.Intravenous bisphosphonate, strontium or fluoride administered for osteoporosis within 5 years of screening 10.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 can be enrolled 11.Ongoing use of any osteoporosis treatment (excluding calcium and vitamin D supplements) taken within the past 5 years prior to screening, with the exception of the medications listed below that are required to adhere to rules for the following wash out periods: •Tibolone, oestrogen/progesterone containing products including any oestrogen/progesterone contraceptives or hormone-replacement therapy, selective oestrogen receptor modulators, received within 3 months prior to screening •Calcitonin, calcitriol, maxacalcitol, falecalcitriol, or alfacalcidol: dose received within 3 months prior to screening •Cinacalcet: dose received within 3 months prior to screening •Parathyroid hormone or parathyroid hormone derivatives within the last 3 months before initial administration of the study drug. 12.Other bone active drugs within the past 3 months before initial administration of the study drug 13.Systemic glucocorticosteroids within the past 3 months before screening 14. Use of certain immunosuppressants within the past 3 months prior to screening 15. Chronic treatment of protein pump inhibitors if used continuously for longer than a year within the past 3 months prior to screening. 16.Use of other investigational drugs within five half-lives of the drug or until the expected PD effect of the drug has returned to baseline or within 30 days prior to screening, whichever is longer, or longer if required by local regulations 17.Oral or dental conditions 18.Vitamin D deficiency (25-OH vitamin D serum level <20 ng/mL). Vitamin D repletion is permitted at the investigator’s discretion and subjects will be rescreened to re evaluate vitamin D level post repletion. Vitamin D levels will be re-tested once within the Screening Period 19.Known intolerance to, or malabsorption of calcium or vitamin D supplements 20.History and/or presence of a severe allergic reaction (eg, general anaphylaxis) 21.Has an active infection that required the use of oral antibiotics within 2 weeks or parenteral antibiotics used within 4 weeks prior to randomisation. Has an HBV, HCV, HIV-1/HIV-2 or SARS-CoV-2 positive test result at screening. If a positive test result is obtained, a confirmatory test is required 22.Received a COVID-19 vaccine within 14 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate equivalent efficacy of MB09 to EU Prolia in postmenopausal women with osteoporosis in terms of lumbar spine BMD at Month 12;Secondary Objective: In Main Treatment period: - To assess the efficacy of MB09 to EU Prolia in postmenopausal women with osteoporosis in terms of lumbar spine BMD at Month 6, and hip and femur neck BMD at Month 6 and Month 12. - To assess the PD profile of MB09 to EU-Prolia in postmenopausal women with osteoporosis in terms of sCTX AUEC up to Month 6 and sCTX at Month 12. - To assess the PK profile of MB09 compared with EU Prolia. - To evaluate the safety profile of MB09 compared with EU Prolia. - To assess the immunogenicity of MB09 compared with EU Prolia assessed through antidrug antibodies.;Primary end point(s): Percentage change from baseline (%CfB) in lumbar spine BMD ;Timepoint(s) of evaluation of this end point: After 52 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy profile: Difference in means (MB09 minus EU-Prolia) in composite endpoint of %CfB (zero is taken for anyone who dies) in - (2a) lumbar spine BMD - (3a) hip BMD - (4a) femur neck BMD PD profile: - Ratio of geometric means (MB09/EU Prolia) in sCTX AUEC (0-6 months) PK profile: - AUC0-6 months and Cmax - Ctrough of serum denosumab Safety profile: - Subject incidence of treatment-emergent adverse events - Subject incidence of adverse events of special interest (injection site reaction, drug-related hypersensitivity/allergic reaction, infection, hypocalcaemia, osteonecrosis of the jaw, cellulitis, and other dermatologic reactions) - Subject incidence of clinically significant changes in physical examinations, laboratory safety tests, ECG and vital signs - Subject incidence of deaths and serious adverse events Inmunogenicity profile: Binding and neutralising serum denosumab antibodies ;Timepoint(s) of evaluation of this end point: Efficacy profile: - (2a) after 6 months - (3a) after 6 and 12 months - (4a) after 6 and 12 months PD profile: Mean difference in sCTX at 11 days; 1, 3 and 6 months after the first dose; and 6 months after the second dose of study drug PK profile: - following the first dose. - at Month 6 and Month 12 Safety profile: - up to and including Month 12 - up to and including Month 12 - from baseline and up to and including Month 12 - up to Month 12 Inmunogenicity profile: • From baseline and up to and including Month 12 | — |
Countries
Bulgaria, Czechia, Estonia, Georgia, Hungary, Latvia, Mexico, Poland, Serbia, Ukraine
Contacts
Public ContactAmalia Flórez Igual
mAbxience Research S.L.
Outcome results
None listed