| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Postmenopausal women diagnosed with osteoporosis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Postmenopausal women diagnosed with osteoporosis |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10031285 |
| E.1.2 | Term | Osteoporosis postmenopausal |
| E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To demonstrate equivalent efficacy of MB09 to EU Prolia in postmenopausal women with osteoporosis in terms of lumbar spine BMD at Month 12 |
|
| E.2.2 | Secondary objectives of the trial |
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. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 (based on age rounded down to the nearest year).
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 albumin-adjusted total serum 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.
|
|
| E.4 | Principal 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 prior to randomisation to study drug or is planning to receive a COVID-19 vaccine within 14 days prior to study drug administration at Month 6 or Month 12
23.History and/or presence of significant cardiac disease as per investigator's discretion, including but not restricted to: ECG abnormalities at screening indicating significant risk of safety for subjects participating in the study, history and/or presence of myocardial infarction within 6 months before screening, history and/or presence of NYHA class III or IV heart failure, any unstable pulmonary disease, hematologic, neurological, psychiatric, endocrine, autoimmune disease, gastrointestinal, renal, urinary, skeletal, or dermatologic disease which can be judged as clinically significant at the investigator’s discretion
24. Subject has a history or current evidence of any condition, therapy, lab abnormality or other circumstances that might confound the results of the study, interfere with the subject's ability to comply with the study procedure, or make participation in the study not in the subject's best interest
25.Currently abuses alcohol or drugs, or has a history of alcohol or drug abuse within 12 months prior to the first administration of the study drug
26.Have major surgery (including surgery to bone), or significant traumatic injury occurring within 4 weeks before randomisation or if one is planned during the study
27.Have immobility due to severe or chronically disabling conditions |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Percentage change from baseline (%CfB) in lumbar spine BMD |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | 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
|
|
| E.5.2.1 | 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
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 59 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Mexico |
| Georgia |
| Serbia |
| Bulgaria |
| Estonia |
| Hungary |
| Latvia |
| Poland |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The study will be completed when the last subject completes the End of Study visit or withdraws early from the study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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