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 evaluate the efficacy of ENZ215 when compared to Prolia® in patients with postmenopausal osteoporosis, in terms of change in BMD at the lumbar spine from baseline to Month 12 • To compare the AUEC of sCTX levels from baseline to Month 6
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E.2.2 | Secondary objectives of the trial |
• To compare the change in sP1NP levels from baseline to Month 6 • To compare the change in BMD at lumbar spine from baseline to Month 6 • To compare the change in BMD at total hip and femoral neck from baseline to Month 6 and Month 12 • To compare the immunogenicity potential of ENZ215 and Prolia® • To compare the safety and tolerability of ENZ215 and Prolia® • To compare the pharmacokinetics of ENZ215 and Prolia® |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Postmenopausal women aged ≥ 55 and ≤ 85 years 2. Body weight ≥ 50 kg and ≤ 90 kg 3. Diagnosed with osteoporosis, with absolute BMD consistent with T-scores of ≤ -2.5 and ≥ - 4.0 at the lumbar spine (L1-L4 region) as measured by dual-energy X ray absorptiometry (DXA) at screening 4. At least 5 years of postmenopausal status confirmed by follicle-stimulating hormone (FSH) levels at screening 5. At least one hip joint and two vertebrae in L1-L4 region evaluable by DXA
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E.4 | Principal exclusion criteria |
1.Previous exposure to Prolia® or any other denosumab biosimilar 2.Previous use of oral bisphosphonates: a.Used for 3 or more years cumulatively b.If used for < 3 years, use within the past 12 months prior to screening 3. Use of intravenous bisphosphonates within the past 5 years prior to screening 4.Use of parathyroid hormone or its derivatives, systemic hormone replacement therapy, selective estrogen-receptor modulators, or tibolone or calcitonin within 12 months prior to enrollment 5.Any prior use of fluoride or strontium 6.Systemic glucocorticoids (≥ 5 mg prednisone equivalent per day or cumulative dose ≥ 50 mg) for more than 10 days within 3 months prior to enrollment 7.Other bone active drugs (i.e. drugs affecting bone metabolism) including heparin, anti epileptics (except for benzodiazepines and pregabalin), antidepressants such as SSRIs, SNRIs, antipsychotics, systemic ketoconazole, ACTH, lithium, protease inhibitors, GnRH agonists, or anabolic steroids within the past 3 months prior to screening or requiring treatment with these agents during the study 8.History of one severe or more than two moderate vertebral fractures per Genant classification as determined by the central reading center 9.History of hip fracture or bilateral hip replacement 10.Total hip or femoral neck T-score <-4.0 11.History and/or presence of atypical femoral fracture 12.Presence of any active healing fracture according to the Investigator’s assessment 13.History of any transplant or chronic immunosuppression 14.Severe liver dysfunction ([ALT] or [AST] > 3 times upper limit of normal) 15.Positive testing for hepatitis B ([HbsAg]) or hepatitis C ([HCV Ab]) virology 16.Known history of human immunodeficiency virus (HIV) infection or positive serology for HIV at screening 17.Significantly impaired renal function (determined by glomerular filtration rate of < 45 mL/min/1.73 m2 by the Modification of Diet in Renal Disease (MDRD) formula, as calculated by the central laboratory) or receiving dialysis 18.Oral or dental conditions: a.Osteomyelitis or history and/or presence of osteonecrosis of the jaw (ONJ) b.Presence of risk factors for ONJ c.Active dental or jaw condition which requires oral surgery d.Planned invasive dental procedure 19.Clinically significant leukopenia, neutropenia, or anemia as determined by the Investigator or any other clinically significant medical condition or laboratory abnormality that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with adherence to study procedures, study completion, or the interpretation of study results 20.Patient with an active infection or history of infection as follows: a.Any active infection for which systemic anti-infectives were used within 4 weeks prior to randomization b.A serious infection defined as requiring hospitalization or intravenous anti infectives within 8 weeks prior to ranomization c.Recurrent or chronic infections or other active infection that, in the opinion of the Investigator, might compromise the safety of the patient 21.Evidence of any of the following conditions per laboratory test results, medical history, electrocardiogram (ECG), DXA, or X-ray review: a.Uncontrolled hyperthyroidism or hypothyroidism b.History or current hyperparathyroidism or hypoparathyroidism (intact parathyroid hormone levels not within normal range) c.Vitamin D deficiency defined as 25 (OH) vitamin D level < 20 ng/mL (< 50 nmol/L) d.Current hypocalcemia (albumin-adjusted serum calcium < 8.0 mg/dL [< 2.0 mmol/L]) or hypercalcemia (albumin-adjusted serum calcium > 10.6 mg/dL [> 2.62 mmol/L]) e.Any bone or metabolic disease which may affect BMD or interfere with the interpretation of the findings, e.g., osteomalacia, osteogenesis imperfecta, osteopetrosis, achondroplasia, Paget’s disease, rheumatoid arthritis, ankylosing spondylitis, Cushing’s disease, hyperprolactinemia, or malabsorption syndrome f.Known or suspected history of alcoholism or substance abuse within the past 12 months prior to the first dosing that the Investigator believes would interfere with understanding or completing the study g.Current heavy smoking, defined as smoking 20 or more cigarettes per day h.History and/or presence of significant cardiac disease as per Investigator’s discretion, including but not restricted to: i.History of cardiac arrhythmia or long QT syndrome or ECG abnormalities at screening indicating significant risk for safety (e.g., that required hospitalization, emergency cardioversion, or defibrillation) ii.History and/or presence of myocardial infarction within 6 months before screening iii.History and/or presence of New York Heart Association (NYHA) class III or IV heart failure i.Suspected signs and symptoms of COVID-19/confirmed COVID-19 or with recent history of travel/contact (less than 2 weeks from screening) with any COVID-19 positive patient/isolation/quarantine
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E.5 End points |
E.5.1 | Primary end point(s) |
• Percentage change in BMD at lumbar spine (L1-L4 region) measured by DXA from baseline to Month 12 • AUEC of sCTX over the initial 6 months (from Day 1 pre-dose to Month 6 pre dose)
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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) |
• Percentage change in sP1NP concentrations from baseline to Month 1, Month 3, and Month 6 • Percentage change in BMD at lumbar spine measured by DXA from baseline to Month 6 • Percentage change in BMD at total hip and femoral neck measured by DXA from baseline to Month 6 and Month 12 • ADAs incidence at baseline (Day 1) and Months 1, 3, 6, 9, and 12 and during open label switch over period, i.e. Months 15 and 18 • Treatment emergent serious and non serious adverse events (TEAEs) during main treatment period and open label switch over period • Alteration in clinical laboratory parameters during main treatment period and open-label switch over period • PK Parameters (Cmax, Tmax, partial AUC(0-1 month), AUC(0-6month)) of denosumab measured at baseline (Day 1), Day 8, Day 15, Month 1, Month 3, Month 6 (prior to second dose), and Month 12 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Percentage change in sP1NP concentrations from baseline to Month 1, Month 3, and Month 6 • Percentage change in BMD at lumbar spine measured by DXA from baseline to Month 6 • Percentage change in BMD at total hip and femoral neck measured by DXA from baseline to Month 6 and Month 12 • ADAs incidence at baseline (Day 1) and Months 1, 3, 6, 9, and 12 and during open label switch over period, i.e. Months 15 and 18 • PK Parameters (Cmax, Tmax, partial AUC(0-1 month), AUC(0-6month)) of denosumab measured at baseline (Day 1), Day 8, Day 15, Month 1, Month 3, Month 6 (prior to second dose), and Month 12 |
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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 | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 |
Serbia |
Bulgaria |
Czechia |
Denmark |
Lithuania |
Poland |
Spain |
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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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The EOS is defined as the date of the last visit of the last patient in the study or last scheduled procedure shown in the schedule of activities (SoA) for the last patient in the study globally.
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 |