E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031282 |
E.1.2 | Term | Osteoporosis |
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 effect of treatment with romosozumab for 12 months compared with placebo on percent changes in bone mineral density (BMD) at the lumbar spine as assessed by dual energy x ray absorptiometry (DXA) in men with osteoporosis. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of treatment with romosozumab for 12 months compared with placebo on the percent changes in DXA BMD at the total hip and femoral neck
- To evaluate the effect of treatment with romosozumab for 6 months compared with placebo on the percent changes in DXA BMD at the lumbar spine, total hip, and femoral neck
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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 |
Bone biopsy sub-study to assess the effect of romosozumab compared
with placebo on parameters of bone histology and histomorphometry |
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E.3 | Principal inclusion criteria |
- Subject has provided informed consent prior to initiation of any study specific activities/procedures
- Ambulatory male subjects ≥ 55 years to ≤ 90 years of age, at the time of enrollment
- Increased risk of fracture, defined as:
* BMD T-score ≤ -2.50 at the lumbar spine, total hip, or femoral neck, based on DXA scans
OR
* BMD T-score ≤ -1.50 at the lumbar spine, total hip, or femoral neck, based on DXA scans and a history of fragility nonvertebral fracture or vertebral facture (thoracic or lumbar)
- Subject has at least 2 evaluable vertebrae in the L1 to L4 region, as assessed by the principal investigator or designee
- Subject has at least 1 evaluable hip, as assessed by the principal investigator or designee |
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E.4 | Principal exclusion criteria |
- BMD T-score ≤ -3.50 at the total hip or femoral neck, as assessed by the central imaging vendor at the time of screening, based on DXA scans
- History of hip fracture
- Oral bisphosphonates:
* any dose received within 3 months prior to randomization
* more than 1 month of cumulative use between 3 and 12 months prior to randomization
* more than 3 years of cumulative use, unless last dose received ≥ 5 years prior to randomization
- Intravenous (IV) bisphosphonates
* Zoledronic acid:
o any dose received within 3 years prior to randomization
o more than 1 dose received within 5 years prior to randomization
IV ibandronate, IV pamidronate, or IV alendronate:
o any dose received within 12 months prior to randomization
o more than 3 years of cumulative use, unless last dose received ≥ 5 years prior to randomization
- Teriparatide or any parathyroid hormone (PTH) analogs:
* any dose received within 3 months prior to randomization
* more than 1 month of cumulative use between 3 and 12 months prior to randomization
- Strontium ranelate, or fluoride (for osteoporosis): more than 1 month of cumulative use within 5 years prior to randomization
- Denosumab or any cathepsin K inhibitor, such as odanacatib (MK-0822): any dose received within 18 months prior to randomization
- Tibolone, cinacalcet, or calcitonin: any dose received within 3 months prior to randomization
- Systemic glucocorticosteroids: ≥ 5 mg prednisone equivalent per day for more than 14 days within 3 months prior to randomization
- Anabolic steroids: any use within 6 months prior to randomization. Testosterone is permitted providing treatment was not begun within the 6 months prior to randomization
- Hormonal ablation therapy: more than 1 month of cumulative use within 6 months prior to randomization
- History of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of the results, such as sclerosteosis, Paget’s disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing’s disease, hyperprolactinemia, and malabsorption syndrome
- Subject with reported history of hearing loss associated with cranial nerve VIII compression due to excessive bone growth (eg, as seen in conditions such as Paget’s disease, sclerosteosis, and osteopetrosis)
- History of solid organ or bone marrow transplant
- Vitamin D insufficiency (defined as 25 (OH) vitamin D levels < 20 ng/ml as determined by the central laboratory). Vitamin D repletion will be permitted and subjects may be rescreened
- Current, uncontrolled hyper- or hypothyroidism, per subject report or chart review. Uncontrolled hyperthyroidism is defined as TSH and T4 outside the normal range. Uncontrolled hypothyroidism is defined as TSH > 10
- Current, uncontrolled hyperparathyroidism or history of hypoparathyroidism, per subject report or chart review. Uncontrolled hyperparathyroidism is defined as:
* PTH outside the normal range in subjects with concurrent hypercalcemia; or PTH values > 20% above the upper limit of normal (ULN) in normocalcemic subjects
- Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range, as assessed by the central laboratory.
- Subject previously has entered this study or has previously participated in a study with a sclerostin antibody product
- Malignancy within the last 5 years, except non-melanoma skin cancers
- Possible diagnosis of multiple myeloma or related lymphoproliferative disorder, as assessed by serum protein electrophoresis performed by the local laboratory (electrophoresis results within 6 months of signing consent will be acceptable)
- Currently receiving treatment in another investigational device or drug study
- Other investigational procedures while participating in this study are excluded
- Positive for hepatitis B, hepatitis C, chronic hepatitis C, and negative viral load while receiving treatment for hepatitis Cas assessed by the central laboratory
- Positive results for human immunodeficiency virus (HIV), per subject report or chart review
- Subject has known sensitivity to any of the products to be administered during dosing (calcium supplements, vitamin D products, or mammalian cell derived products)
- Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator’s knowledge
- History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in DXA BMD at the lumbar spine at month 12 |
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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) |
- Percent change from baseline in DXA BMD at the femoral neck and total hip at month 12
- Percent change from baseline in DXA BMD at the lumbar spine, femoral neck, and total hip at month 6
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Bone biopsy sub-study to assess the effect of romosozumab compared with placebo on parameters of bone histology and histomorphometry |
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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) | No |
E.8.2.2 | Placebo | Yes |
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 | 16 |
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 |
Belgium |
Colombia |
Czech Republic |
Denmark |
Japan |
Mexico |
Poland |
Russian Federation |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
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 | 1 |