Postmenopausal osteoporosis MedDRA version: 20.0 Level: PT Classification code 10031285 Term: Osteoporosis postmenopausal System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Gedeon Richter Plc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant is = 60 to = 90 years of age at the time of signing the informed consent. 2. Participant is an ambulatory postmenopausal woman, diagnosed with osteoporosis, able to walk and not bedridden. A woman is considered postmenopausal if she meets any of the following criteria: a. Has 12 months of spontaneous amenorrhea without an alternative medical cause with serum follicle stimulating hormone (FSH) levels falling in the normal postmenopausal range at the central laboratory at the time of the Screening Period. b. Female participant underwent bilateral oophorectomy (with or without hysterectomy) at least 6 weeks prior to the Screening Period. 3. Participant has an absolute BMD consistent with T score = 2.5 and = 4.0 at the lumbar spine as measured by dual energy X ray absorptiometry (DXA) during the Screening Period and at least 2 lumbar vertebrae (from L1 to L4) must be evaluable by DXA. 4. Participant has body weight = 50 and = 90 kg at the Screening Period. 5. Participant is willing and able to give signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. 6. Participant has provided informed consent prior to any study specific activities/procedures. Participant must meet the following criteria to be enrolled in the Transition Period: 7. Have been enrolled, received both doses of IMP and completed the scheduled Main Period (up to Week 52) of the RGB-14-101 study. 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 108 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 326
Exclusion criteria
Exclusion criteria: 1. Participant has a 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. 2. Participant has a history and/or presence of hip fracture. 3. Participant has a history and/or presence of atypical femur fracture. 4. Participant presents with an active healing fracture according to the assessment of the Investigator. 5. Participant has a bilateral hip replacement (unilateral is allowed if the other hip is evaluable with DXA). 6. Participant has a vitamin D deficiency, the assessment may be repeated once after vitamin D supplementation. Appropriate vitamin D dosing in addition to vitamin D supplementation is permitted at the discretion of the Investigator during the Screening Period. 7. Participant has hypocalcaemia or hypercalcaemia at the Screening Period, the assessment may be repeated once in the case of hypercalcaemia. 8. Participant has a history and/or presence of bone metastases, renal osteodystrophy, osteomyelitis, any metabolic, endocrine or traumatic bone disease (except postmenopausal osteoporosis) that may interfere with the interpretation of the results. 9. Participant has a current uncontrolled status of hypothyroidism or hyperthyroidism. 10. Participant has a history (within 5 years prior to Screening) and/or current hypoparathyroidism or hyperparathyroidism other than clinically not significant secondary hyperparathyroidism. 11. Participant has had major surgery within 8 weeks prior to the Screening Period or planned, anticipated major surgery during the study. 12. Participant has malignancy within 5 years before Screening (except completely cured in situ cervical carcinoma or non metastatic squamous or basal cell carcinoma of the skin). 13. Participant has a history and/or presence of significant cardiac disease or ECG abnormalities indicating significant risk for participating in the study as judged by the Investigator. 14. Participant has a known intolerance or malabsorption of calcium or vitamin D supplements. 15. Participant has a known hypersensitivity (including severe allergic reaction) to monoclonal antibodies or a history of systemic hypersensitivity to any components of the IMPs. 16. Participant shows contraindications to denosumab therapy (e.g., hypocalcaemia), or calcium or vitamin D supplementation before starting IMP administration. 17. Participant has a latex allergy. 18. Participant has a history and/or presence of ONJ or risk factors for ONJ. 19. Participant has history and/or presence of osteonecrosis of the external auditory canal. 20. Participant requiring ongoing use of any osteoporosis treatment (other than calcium and vitamin D supplements). 21. Participant has previously received denosumab or biosimilar denosumab. 22. Participant has previously received any of medicines listed in protocol. 23. Participant is receiving or has received any investigational drug (or is currently using an investigational device) within 3 months before receiving IMP, or at least 10 times the respective elimination half life (whichever period is longer). 24. Participant has weight or girth measurements which may preclude accurate DXA measurements in Investigator’s opinion. 25. Participant has inadequate renal and hepatic function at the Screening Period defined as patient on dialysis or estimated glomerular filtration rate (eGFR) < 30 mL/min (calculated using the modification of diet in renal disease [MDRD] f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy To demonstrate similar efficacy and effect of RGB 14 P with US licensed Prolia® on BMD at the lumbar spine at Week 52 in female participants with postmenopausal osteoporosis Pharmacodynamics To demonstrate similar pharmacodynamics (AUEC of %CfB in sCTX) of RGB 14 P with US licensed Prolia® in female participants with postmenopausal osteoporosis (only required for EMA) ;Secondary Objective: Efficacy To provide additional comparative efficacy data of RGB 14 P with US licensed Prolia® in female participants with postmenopausal osteoporosis Pharmacodynamics To provide additional comparative pharmacodynamic data of RGB 14 P with US licensed Prolia® in female participants with postmenopausal osteoporosis Safety To compare the safety and tolerability of RGB 14 P with US licensed Prolia® in female participants with postmenopausal osteoporosis Immunogenicity To compare the immunogenicity of RGB 14 P with US licensed Prolia® in female participants with postmenopausal osteoporosis ;Primary end point(s): Efficacy %CfB in lumbar spine BMD Pharmacodynamics AUEC of %CfB sCTX0-m6 ;Timepoint(s) of evaluation of this end point: Efficacy %CfB in lumbar spine BMD at Week 52 Pharmacodynamics AUEC of %CfB sCTX0-m6 until Week 26 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy •%CfB in total hip BMD •%CfB in lumbar spine BMD •%CfB in femoral neck BMD •Vertebral fragility fracture incidence •Non vertebral fragility fracture incidence Pharmacodynamics •%CfB in serum P1NP •%CfB in sCTX Safety •AE, SAE, clinical laboratory safety assessments (haematology, clinical chemistry and urinalysis), vital signs, physical examination, ECG and injection site reaction Immunogenicity •Incidence of binding ADAs and NAbs •Titer determination of binding ADAs ;Timepoint(s) of evaluation of this end point: Efficacy •%CfB in total hip BMD at Weeks 26, 52 and 78 •%CfB in lumbar spine BMD at Weeks 26 and 78 •%CfB in femoral neck BMD at Weeks 26, 52 and 78 •Vertebral fragility fracture incidence at Weeks 52 and 78 •Non vertebral fragility fracture incidence at Weeks 52 and 78 Pharmacodynamics •%CfB in serum P1NP at Weeks 4, 26, 52 and 78 •%CfB in sCTX at Weeks 4, 26, 52 and 78 Safety •AE, SAE, clinical laboratory safety assessments (haematology, clinical chemistry and urinalysis), vital signs, physical examination, ECG and injection site reaction up to Week 78 Immunogenicity •Incidence of binding ADAs and NAbs at Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78 •Titer determination of binding ADAs at Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78 | — |
Countries
Bulgaria, Czechia, Czech Republic, Hungary, Italy, Poland, Spain, Ukraine, United States
Contacts
Public ContactMedical Information Service
Gedeon Richter Plc.
Outcome results
None listed