E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of postmenopausal osteoporosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031285 |
E.1.2 | Term | Osteoporosis postmenopausal |
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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 |
The primary objective is to determine whether Denosumab (formaerly known as AMG 162) treatment can reduce the number of postmenopausal osteoporotic women (BMD T-score below -2.5) with new vertebral fractures as compared with control (placebo plus vitamin D and calcium).
The primary safety objective is to characterize the safety and tolerability profile of denosumab in this population based on the adverse event incidence, changes in laboratory profiles, and immunogenicity to denosumab . |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives will be to assess the effect of denosumab on time to first non-vertebral fracture and time to first hip fracture. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. DXA substudy - The effect of denosumab on BMD measured at the lumbar spine, proximal femur (total hip, femoral neck, and trochanter), distal 1/3 radius, and total body (7 May 2004)
2. Bone and cartilage marker substudy - The effect of denosumab on bone turnover, measured by serum Type I C-Telopeptide (CTX), procollagen Type I N-terminal peptide (PINP), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase 5b (TRAP-5b); and cartilage degradation, measured by urine Type II CTX/creatinine levels (7 May 2004)
3. QCT of the spine and hip substudy - The effect of denosumab on trabecular and cortical bone as assessed by quantitative computerized tomography (QCT) of the lumbar spine and hip (7 May 2004)
4. QCT of the distal radius substudy - The effect of denosumab on peripheral trabecular and cortical bone as assessed by quantitative computerized tomography (QCT) of the distal radius (7 May 2004)
5. Transiliac bone biopsy substudy - The effect of denosumab on bone histology and histomorphometry based on transiliac bone biopsies and the effect of denosumab on bone micro-architecture based on micro-CT of transiliac bone biopsies (7 May 2004)
6. Pharmacokinetic substudy - The pharmacokinetics of denosumab using population pharmacokinetic analysis methods and serum denosumab data collected through sparse sampling (19 Dec 2005)
7. Fracture healing substudy - The effect of denosumab on the healing of distal radius fractures (19 Dec 2005)
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E.3 | Principal inclusion criteria |
- Postmenopausal, ambulatory women, between 60 and 90 years old - BMD T-score < –2.5 at one or more of the following regions: the lumbar spine or total hip - Ethical - Before any study-specific procedure, the appropriate written informed consent must be obtained
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E.4 | Principal exclusion criteria |
- BMD T-score < -4.0 at one or more of the following regions: Lumbar spine or total hip - Oral bisphosphonate treatment for osteoporosis: Ineligible if used for 3 or more years cumulatively; If used for >3 months, but ≤ 3 years, at least a one year period since last dose is necessary for eligibility; If used ≤ 3 months at any time in the past, subject is eligible. - Administration of intravenous bisphosphonate, fluoride or strontium for osteoporosis within the last 5 years - Administration of any of the following treatments within the last 6 weeks: a) PTH or PTH derivatives, eg, teriparatide b) Anabolic steroids or testosterone c) Glucocorticosteroids (> 5 mg prednisone equivalent per day for more than 10 days) d) Systemic hormone replacement therapy e) Selective estrogen receptor modulators (SERMs), eg, raloxifene f) Tibolone g) Calcitonin h) Calcitriol - Evidence of any of the following per patient report, chart review, DXA, or X-ray review: a) Hyper or hypothyroidism; patients on stable thyroid treatment with a normal TSH will be allowed b) Current hyper- or hypoparathyroidism c) Current hypocalcemia (albumin adjusted serum calcium below 2.13 mmol/L [8.5 mg/dL]) d) Vitamin D deficiency [(25) hydroxy Vitamin D level < 12 ng/mL) e) Rheumatoid arthritis f) Paget’s disease g) Malignancy (except basal cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years h) Any bone disease, eg, osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings i) Malabsorption syndrome j) Height, weight and girth which may preclude accurate DXA measurements k) Advanced scoliosis or extensive lumbar fusion which would preclude vertebral fracture assessment l) Any severe or more than 2 moderate vertebral fractures on spinal X-rays (see section 7.9 of protocol) m) Less than 2 lumbar vertebrae (L1-L4) evaluable for DXA - Known sensitivity to mammalian cell derived drug products - Any organic or psychiatric disorder, or laboratory abnormality which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results - Evidence of alcohol or substance-abuse within the last 12 months that the investigator believes would interfere with understanding or completing the study - Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures - For biopsy sub study subjects only: known or suspected sensitivity or contraindication to tetracycline derivatives - Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s).
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoints: - Subject incidences of new vertebral fractures (Yes/No) during the entire 36 month treatment period.
Safety Endpoints include: - Adverse events by system organ class and preferred term - Changes in safety laboratory analytes (serum chemistry, hematology) - Number of subjects with anti-denosumab antibodies (Yes/No)
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 152 |
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 | Information not present in EudraCT |
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 |
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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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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 | 3 |
E.8.9.1 | In the Member State concerned months | 10 |
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 | 10 |