E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteoporosis is defined as a progressive, systemic skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis is estimated to affect 200 million women worldwide, approximately one-tenth of women aged 60, one-fifth of women aged 70, and two-fifths of women aged 80 (Johnell and Kanis 2006). |
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E.1.1.1 | Medical condition in easily understood language |
Osteoporosis is defined as a progressive, systemic skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue. |
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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 | 10031282 |
E.1.2 | Term | Osteoporosis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 |
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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 similar efficacy between GP2411 and EU-authorized Prolia, in terms of bone mineral density (EMA, FDA and PMDA) - To demonstrate similar PD between GP2411 and EU-authorized Prolia, in terms of the bone resorption marker CTX (EMA) - To demonstrate similar PK between GP2411 and EU-authorized Prolia (PMDA) |
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E.2.2 | Secondary objectives of the trial |
- To demonstrate similar PD between GP2411 and EU-authorized Prolia, in terms of the bone resorption marker CTX (FDA and PMDA). - To compare GP2411 and EU-authorized Prolia in terms of PK, PD, efficacy, safety and immunogenicity. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study must meet all of the following criteria: 1. Signed informed consent must be obtained prior to participation in the study. 2. Postmenopausal women, diagnosed with osteoporosis. Postmenopausal status is defined as at least 12 consecutive months of amenorrhea prior to date of screening, for which there is no other obvious pathological or physiological cause. [For CZ only: Postmenopausal status is defined as at least 12 consecutive months of amenorrhea prior to date of screening for which there is no other obvious pathological or physiological cause and by elevated serum follicle-stimulating hormone (FSH) level assessed by central laboratory at screening]. 3. Aged ≥ 55 and ≤ 80 years at screening 4. Body weight ≥ 50 kg and ≤ 90 kg at screening 5. Absolute bone mineral density consistent with T-score ≤ -2.5 and ≥ -4.0 at the lumbar spine as measured by DXA during the Screening Period 6. At least two vertebrae in the L1-L4 region (wertebrae 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 |
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E.4 | Principal exclusion criteria |
Patients meeting any of the following criteria are not eligible for inclusion in this study. 1. Use of other investigational drugs within 5 half-lives of the drug or until the expected pharmacodynamic effect of the drug has returned to baseline, whichever is longer, or longer if required by local regulations. 2. Previous exposure to denosumab (Prolia, Xgeva, or biosimilar denosumab). 3. History of hypersensitivity to any recombinant protein drugs or any of the excipients used in GP2411 or Prolia (excipients detailed in Table 6- 1). 4. History and/or presence of one severe or more than two moderate vertebral fractures (as determined by central reading of lateral spine Xray during the Screening Period). 5. History and/or presence of hip fracture. 6. Presence of active healing fracture according to assessment of investigators. 7. History and/or presence of bone metastases (see also exclusion criterion #25), bone disease, metabolic disease (except osteoporosis) that may interfere with the interpretation of the results, e.g. Paget's disease, rheumatoid arthritis, ankylosing spondylitis, osteomalacia, osteogenesis imperfecta, osteopetrosis, Cushing's disease, hyperprolactinemia or malabsorption syndrome. 8. Ongoing use of any osteoporosis treatment (other than calcium and vitamin D supplements). Following rules for wash-out periods for osteoporosis treatments have to be adhered to: - Drugs being investigated for osteoporosis, e.g. romosozumab: dose received at any time - Strontium or fluoride (for osteoporosis): dose received at any time - Intravenous bisphosphonates: dose received within 5 years prior to screening - Oral bisphosphonates - > 3 years of cumulative use prior to screening - any dose received within 12 months prior to screening - Teriparatide or any PTH analogs: dose received within 12 months prior to screening - Tibolone, oral or transdermal estrogen, selective estrogen receptor modulators: dose received within 12 months prior to screening - Calcitonin: dose received within 6 months prior to screening - Cinacalcet: dose received within 3 months prior to screening. XML File Identifier: LRJA1mnSbr2JIcq9ddLrnYxfkvs= Page 15/25 9. Systemic glucocorticosteroids (≥ 5 mg prednisone equivalent per day for ≥ 10 days or a total cumulative dose of ≥ 50 mg) within the past 3 months before screening. 10. Other bone active drugs including heparin, anti-convulsives (with the exception of benzodiazepines), systemic ketoconazole, adrenocorticotropic hormone, lithium, gonadotropin releasing hormone agonists, anabolic steroids, within the past 3 months before screening. 11. Oral or dental conditions: - osteomyelitis or history and/or presence of osteonecrosis of the jaw (ONJ) - presence of risk factors for ONJ (e.g. periodontal disease, poorly fitting dentures, invasive dental procedures such as tooth extractions in 6 months before screening) - active dental or jaw condition which requires oral surgery - planned invasive dental procedure. 12. Current uncontrolled status of hypothyroidism or hyperthyroidism. 13. History and/or current hypoparathyroidism or hyperparathyroidism, irrespective of current controlled or uncontrolled status. 14. Vitamin D deficiency (25 [OH] vitamin D serum level <50 nmol/L [<20 ng/mL]). An Appropriate vitamin D dose in addition to vitamin D supplementation is permitted at the investigator's discretion and patients will be retested during the screening period or may be rescreened . 15. Current hypocalcemia, defined as calcium <2.10 mmol/L [<8.42mg/dL] or hypercalcemia, defined as calcium >2.62 mmol/L [>10.50 mg/dL]; patients must have normal albumin values (32-55 g/L [3.2-5.5 g/dL]) according to central laboratory normal range. 16. Known intolerance to, or malabsorption of calcium or vitamin D supplements. 17. History and / or presence of a severe allergic reaction (e.g. anaphylaxis). 18. 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 patients 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. 19. Patients having at screening any of the following hematology values: - Hemoglobin < 10.0 g/dL [<100 g/L] - White blood cell (WBC) count < 3,500/μL [< 3.5 x 109 /L], or neutrophil count < 2,000/μL [< 2.0 x 109 /L], or platelet count < 125,000/μL [< 125 x 109 /L]. 20. Renal impairment manifesting with an estimated glomerular filtration rate (eGFR) < 45 ml/min. Other protocol-defined exclusion criteria may apply (please see protocol section 5.2 for full exclusion list).
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E.5 End points |
E.5.1 | Primary end point(s) |
- Percent change from baseline (%CfB) in lumbar spine BMD (LS-BMD) - Area under the effective curve (AUEC) of %CfB in serum CTX (only EMA) - Serum PK parameters AUCinf and Cmax |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- %CfB in LS-BMD at week 52 (FDA, EMA, PMDA) - AUEC after first dose (until week 26) of %CfB in sCTX - Serum PK parameters AUCinf and Cmax after first dose (until week 26) |
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E.5.2 | Secondary end point(s) |
- AUEC of %CfB in sCTX (FDA, PMDA) - %CfB in BMD at lumber spine, femoral neck and total hip (LS-BMD, FN-BMD, TH-BMD) - PD markers: CTX and procollagen 1 N-terminal propeptide (P1NP) serum concentrations# - Safety : Fractures, vital signs , laboratory safety assessments , injection site reactions, electrocardiogram, (ECG), occurrence of adverse events (AE's) and serious AE's - Immunogenicity: Development of binding and neutralizing anti-drug antibodies (ADAs) - Serum PK parameters AUCinf and Cmax after first dose (only EMA) - Denosumab serum concentrations |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- AUEC after first dose (until week 26) of %CfB in sCTX (FDA, PMDA) - %CfB in LS-BMD, FN-BMD and TH-BMD at week 26, week 52 and week 78 - PD markers: CTX and procollagen 1 N-terminal propeptide (P1NP) serum concentrations as per visit schedule from week 52 to week 78 - Safety : Fractures, vital signs , laboratory safety assessments , injection site reactions, electrocardiogram, (ECG), occurrence of adverse events (AE's) and serious AE's from week 52 to week 78 - Immunogenicity: Development of binding and neutralizing anti-drug antibodies (ADAs) from week 52 to week 78 - Serum PK parameters AUCinf and Cmax after first dose (up until week 26, only EMA) - Denosumab serum concentrations as per visit schedule from week 52 to week 78 |
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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 | Yes |
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 |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | Yes |
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 | 2 |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 |
Japan |
United States |
Bulgaria |
Poland |
Spain |
Czechia |
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E.8.7 | Trial has a data monitoring committee | No |
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
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Study completion is defined as the date when the last patient finishes the End of Study Visit/Early Termination Visit, or the date at which the last data point from the last patient is received, whichever is later. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |