E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteoporosis in Postmenopausal Women |
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E.1.1.1 | Medical condition in easily understood language |
Osteoporosis (a disease that makes bone fragile) in who have been through the menopause |
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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 | HLT |
E.1.2 | Classification code | 10005992 |
E.1.2 | Term | Bone metabolism disorders |
E.1.2 | System Organ Class | 100000004861 |
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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 equivalent efficacy of the proposed biosimilar denosumab FKS518 to US-licensed Prolia (US-Prolia) in women with postmenopausal osteoporosis (PMO). For Marketing Authorization Application (MAA) in the European Union (EU) and European Economic Area (EEA) only: to demonstrate equivalent efficacy and pharmacodynamics (PD) of the proposed biosimilar denosumab FKS518 to US- licensed Prolia (US-Prolia) in women with PMO. |
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E.2.2 | Secondary objectives of the trial |
To compare the safety, tolerability, PD and immunogenicity of FKS518 to US-Prolia in women with PMO. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Female ≥55 to ≤85 years of age, inclusive, at screening. 2. Subject should have confirmed postmenopausal status, defined as age-related or early/premature amenorrhea ≥12 consecutive months and increased follicle-stimulating hormone (FSH) >40 mIU/mL at screening; or surgical menopause (bilateral oophorectomy with or without hysterectomy) ≥12 months prior to screening. 3. Absolute BMD consistent with T-score ≤-2.5 and ≥-4.0 at the lumbar spine as measured by DXA as per central assessment. 4. At least 2 vertebrae in the L1-L4 region and at least 1 hip joint are evaluable by DXA.
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E.4 | Principal exclusion criteria |
1. History and/or presence of 1 severe or >2 moderate vertebral fractures or hip fracture confirmed by x-ray. 2. Presence of active healing fracture at screening. 3. History and/or presence of bone-related disorders, such as but not limited to Paget’s disease, osteomalacia, hyperparathyroidism (or parathyroid disorders), or renal osteodystrophy. 4. Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures, poor oral hygiene, periodontal, and/or pre-existing dental disease as assessed by the Investigator. 5. Prior denosumab (Prolia, Xgeva, or proposed denosumab biosimilar) exposure. 6. Prior use of fluoride within the 5 years before inclusion in the study. 7. Any current or prior use of strontium ranelate.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: • Percent change from baseline in LS-BMD by DXA at Week 52. • Area under the effect curve (AUEC) of serum CTX up to Week 26 (for MAA in the EU and EEA only). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline up to Week 26 and to Week 52 |
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E.5.2 | Secondary end point(s) |
Efficacy: • Percent change from baseline in BMD at femoral neck and total hip by DXA at Week 52. Pharmacodynamic: • Percent change from baseline in serum P1NP at Week 52. • Percent change from baseline in serum CTX at Week 52. Safety and tolerability: • Occurrence of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) during Core Treatment Period, Transition Period, and overall. • Occurrence of treatment-emergent adverse events of special interest (AESIs): drug-related hypersensitivity/allergic reactions (Common Terminology criteria for Adverse Events [CTCAE] Grade ≥3 or reported as SAEs), and adverse events leading to IP discontinuation or study withdrawal during Core Treatment Period, Transition Period, and overall. • Occurrence of injection site reactions (local tolerability) during Core Treatment Period, Transition Period, and overall. Immunogenicity: • Antidrug antibody (ADA) incidence during Core Treatment Period, Transition Period, and overall. • ADA titer during the Core Treatment Period, Transition Period. • Neutralizing antibody (NAb) incidence during the Core Treatment Period, Transition Period, and overall. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 52, Week 72 and overall |
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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 | 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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
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 |
Georgia |
Bulgaria |
Czechia |
Estonia |
Hungary |
Poland |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 15 |