E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal osteoporosis |
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E.1.1.1 | Medical condition in easily understood language |
Osteoporosis in women after menopause |
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E.1.1.2 | Therapeutic area | Body processes [G] - Bones and nerves physological processes [G11] |
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 |
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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 the equivalence of SB16 to Prolia®, in terms of percent change from baseline in lumbar spine bone mineral density (BMD) at Month 12 in subjects with postmenopausal osteoporosis (PMO). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of SB16 compared to Prolia® by -Percentage change from baseline in lumbar spine BMD -Percentage change from baseline in total hip BMD -Percentage change from baseline in femoral neck BMD To evaluate the safety and tolerability of SB16 compared to Prolia® To evaluate the pharmacokinetic (PK) profile of SB16 compared to Prolia® To evaluate the pharmacodynamic (PD) profile of SB16 compared to Prolia® To evaluate the immunogenicity of SB16 compared to Prolia® To evaluate the safety, tolerability, immunogenicity, PK, PD, and efficacy in subjects with PMO who transitioned to SB16 from Prolia® compared to subjects who maintained Prolia® from the Main period |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following criteria to be eligible for the study: 1.Postmenopausal women (defined as lack of menstrual period for at least 12 months prior to Screening, for which there is no other pathological or physiological cause) who are 55 to 80 years of age at Screening Serum follicle stimulating hormone (FSH) test can be done at Screening in case of uncertainty. 2.Ambulatory and visually unimpaired to participate in the study at Screening, in the opinion of the Investigator 3.Absolute BMD consistent with T-score at the total hip or lumbar spine of ≥ ‒4 and ≤ ‒2.5, determined by central imaging centre at Screening 4.At least three evaluable vertebrae within L1 to L4, one evaluable femoral neck, and one evaluable hip joint for BMD measurement, determined by central imaging centre at Screening 5.Biologic (defined as any therapeutic monoclonal antibody or fusion receptor protein, including denosumab, denosumab biosimilars, or romosozumab) naïve at Screening 6.Body weight of ≥ 50 kg and ≤ 90 kg at Screening 7.Has provided informed consent voluntarily and must be able to, in the opinion of the Investigator, understand the implications of taking part in the study, be willing to follow the study requirements, and complete the study
Subjects must meet the following criteria to be enrolled in the Transition period: 1.Have been enrolled and completed the scheduled Month 12 of the Main period of the SB16-3001 study
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria are not eligible for the study: 1.One severe or more than two moderate vertebral fractures on spinal X-ray according to Genant classification, determined by central imaging centre at Screening 2.History of hip fracture or bilateral hip replacement at Screening 3.Uncorrected vitamin D deficiency 4.Hypercalcemia or hypocalcaemia at Screening 5.Inadequate haematological function at Screening 6.Inadequate renal or hepatic function at Screening 7.Known allergic reactions, hypersensitivity, or intolerance to denosumab or to any ingredients of the investigational product (IP), including latex allergy or hereditary problems of fructose intolerance at Screening 8.May not tolerate long-term calcium or vitamin D supplementation or subject with malabsorption of calcium or vitamin D supplements, in the opinion of the Investigator, at Screening 9.Use of any of the medications that can affect BMD 10.Use of any non-biologic IP that is not indicated for osteoporosis from another study or use of an investigational device at Screening 11.Non-osteoporosis medical conditions that can affect BMD at Screening
23.Any clinically significant disease or disorder or laboratory abnormality which, in the opinion of the Investigator, would prevent the subject from completing the study or the interpretation of the study results at Screening and Randomisation
Subjects meeting the following criteria must not be enrolled in the Transition period: 1.Found to be of increased risk to continue enrolment, in the opinion of the Investigator
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in lumbar spine BMD
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints for the Main period Efficacy endpoints -Percent change from baseline in lumbar spine BMD -Percent change from baseline in total hip BMD -Percent change from baseline in femoral neck BMD Safety endpoints -Incidence of adverse events (AEs) -Incidence of serious AEs (SAEs) PK endpoint -Serum drug concentration PD endpoints -Serum C-telopeptide of type I collagen (CTX) concentration -Area under the effect curve from time zero to Month 6 (AUECO-M6) of percent change from baseline in serum CTX -Serum procollagen type I N-terminal propeptide (P1NP) concentration Immunogenicity endpoint -Incidence of anti-drug antibodies (ADAs) -Incidence of neutralising antibodies (NAbs)
Secondary endpoints for the Transition period Safety endpoints -Incidence of AEs -Incidence of SAEs Immunogenicity endpoint -Incidence of ADAs and NAbs Efficacy endpoints -Percent change from baseline in lumbar spine BMD -Percent change from baseline in total hip BMD -Percent change from baseline in femoral neck BMD PK endpoint -Serum drug concentration PD endpoint -Serum CTX concentration -Serum P1NP concentration |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints for the Main period Safety endpoints during whole study Efficacy endpoints -Percent change from baseline in lumbar spine BMD at Month 6 -Percent change from baseline in total hip BMD at Month 6 and 12 -Percent change from baseline in femoral neck BMD at Month 6 and 12 PK endpoint at Months 0, 0.5, 1, 3, 6, 9, and 12 PD endpoints -Serum CTX at Months 0, 0.5, 1, 3, 6, 9, and 12 -AUECO-M6 at Month 6 -Serum P1NP at Months 0, 0.5, 1, 3, 6, 9, and 12 Immunogenicity endpoint -Incidence of ADAs and NAbs at Months 0, 0.5, 1, 3, 6, 9, and 12 -Incidence of NAbs at Months 0, 0.5, 1, 3, 6, 9 and 12
Secondary endpoints for the Transition period Safety endpoints during whole study Immunogenicity, efficacy, PK and PD endpoints at Month 18
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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 | No |
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 |
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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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 |
Korea, Republic of |
Lithuania |
Poland |
Bulgaria |
Czechia |
Denmark |
Hungary |
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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
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A subject is considered to have completed the study if she has completed the last scheduled visit or the last scheduled procedure shown in the Schedule of Activities. EOS is defined as completion of the last scheduled visit (Month 18). The end of this clinical study is defined as completion of the last subject’s EOS/ET. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
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 | 8 |