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). MedDRA version: 20.0 Level: PT Classification code 10031282 Term: Osteoporos
Conditions
Interventions
Product Name: Denosumab
Product Code: GP2411
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: denosumab
CAS Number: 615258-40-7
Current Sponsor code: GP2411
Other
Sponsors
Hexal AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects 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. 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 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 157 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 365
Exclusion criteria
Exclusion criteria: Subjects 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 X-ray 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 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 < 20 ng/mL). Vitamin D repletion is permitted and patients will be rescreened to re-evaluate Vitamin D level post repletion 15. Current hypocalcemia or hypercalcemia based on albumin adjusted serum calcium 16. Known intolerance to, or malabsorption of calcium or vitamin D sup
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - 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);Secondary Objective: - 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.;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;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) | — |
Secondary
| Measure | Time frame |
|---|---|
| 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;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 | — |
Countries
Bulgaria, Czech Republic, Hungary, Italy, Japan, Poland, Spain, United States
Contacts
Public ContactClinical Trial Information Desk
Hexal AG
Outcome results
None listed