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 |
Postmenopausal osteoporosis |
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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 | 16.1 |
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 noninferiority of a 6-month treatment with 210 mg romosozumab administered every month (QM) using a 90 mg/mL concentration compared with 210 mg romosozumab QM using a 70 mg/mL concentration on percent changes in bone mineral density (BMD) at the lumbar spine as assessed by dual-energy x-ray absorptiometry (DXA) in postmenopausal women with osteoporosis |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of 6-month treatment with 210 mg romosozumab QM using romo 90 mg/mL and romo 70 mg/mL on:
- percent changes in DXA BMD at the total hip and femoral neck
- percent changes in bone turnover markers (BTM): bone formation marker procollagen type 1 N-telopeptide (P1NP) and bone resorption marker serum type I collagen C-telopeptide (CTX) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject has provided informed consent prior to initiation of any study-specific activities/procedures
• Postmenopausal females (postmenopausal status is defined as no vaginal bleeding or spotting for 12 consecutive months prior to screening)
• ≥ 55 to ≤ 90 years of age, at the time of enrollment
• Ambulatory
• BMD T-score ≤ -2.50 at the lumbar spine, total hip, or femoral neck, as assessed by the central imaging vendor at the time of screening, based on DXA scans
• Subjects has at least two evaluable vertebrae in the L1-L4 region, as assessed by the principal investigator or designee
• Subject has at least one evaluable hip, as assessed by the principal investigator or designee
• Subject has history of fragility (ie, osteoporosis-related) fracture or subject meets at least 2 of the following clinical risk factors for fracture
- ≥ 70 years of age, at the time of enrollment
- BMD T-score ≤ -3.00 at the lumbar spine, total hip, or femoral neck, as assessed by the central imaging vendor at the time of screening, based on DXA scans
- current smoking
- ≥ 3 glasses of alcohol a day
- parental history of fragility (ie, osteoporosis-related) fracture
- body weight ≤ 125 pounds/56 kilogram |
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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
Use of agents affecting bone metabolism
• Strontium ranelate or fluoride (for osteoporosis): more than 1 month of cumulative use within 5 years prior to randomization
• IV bisphosphonates
Zoledronic acid:
- any dose received within 3 years prior to randomization
- more than 1 dose received within 5 years prior to randomization
IV ibandronate or IV pamidronate:
- any dose received within 12 months prior to randomization
- more than 3 years of cumulative use, unless last dose received ≥ 5 years prior to randomization
• Dose received within the past 18 months prior to randomization: denosumab or any cathepsin K inhibitor, such as odanacatib (MK-0822)
• Teriparatide or any 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
• 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
• Dose received within the past 6 months prior to randomization: systemic oral or transdermal estrogen or selective estrogen receptor modulators (SERMs) (up to 1 month of cumulative use is allowed)
• Dose received within the past 6 months prior to randomization: hormonal ablation therapy (up to 1 month of cumulative use is allowed)
• Dose received within the past 3 months prior to randomization: tibolone, calcitonin, or cinacalcet
• Dose received within the past 3 months prior to randomization: systemic glucocorticosteroids (≥ 5 mg prednisone equivalent per day for more than 14 days)
Medical history
• 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 serum 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, defined as thyroid-stimulating hormone and thyroxine outside the normal range, per subject report or chart review
• Current, uncontrolled hyper- or hypoparathyroidism, defined as PTH outside the normal range, per subject report or chart review
• Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range, as assessed by the central laboratory. Serum calcium levels may be retested once in case of an elevated serum calcium level within 1.1x the upper limit of normal (ULN) as assessed by the central laboratory.
• Positive for Hepatitis B
• Positive for Hepatitis C, Chronic Hepatitis C and negative viral load while receiving treatment for Hepatitis C
• Positive for Human Immunodeficiency Virus, per subject report or chart review
• Malignacy within the last 5 years, except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ
General criteria
• Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s).
• Subject has previously entered this study
• Subject has previously participated in a study with a sclerostin antibody product
• Other investigational procedures while participating in this study are excluded
• Subject has known sensitivity or intolerance to any of the products or components to be administered (calcium supplements, vitamin D products, or mammalian cell derived products)
• Subject is pregnant, or might become pregnant within 3 months after the end of treatment, ie, 3 months after the Month 6 study visit
• Subject is breast feeding
• 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 |
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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 total hip
- percent change from baseline in DXA BMD at the femoral neck
- percent change from baseline in BTMs P1NP and CTX |
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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 | 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 | No |
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 | 4 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Poland |
United States |
Czech Republic |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |