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 |
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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 | 19.1 |
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 describe the effect of 12 months of treatment with romosozumab versus alendronate (ALN) on the percent change in dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) at the lumbar spine in postmenopausal women with osteoporosis previously treated with romosozumab followed by ALN sequential therapy. |
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E.2.2 | Secondary objectives of the trial |
• To describe the effect of 12 months of treatment with romosozumab versus ALN in postmenopausal women with osteoporosis previously treated with romosozumab followed by ALN sequential therapy on the following:
o percent change in DXA BMD at the total hip and femoral neck
o percent change in bone turnover markers (BTMs)
• To describe the effect of 12 months of treatment with romosozumab followed by 12 months of ALN versus 24 months of ALN in postmenopausal women with osteoporosis previously treated with romosozumab followed by ALN sequential therapy on the following:
o percent change in DXA BMD at the lumbar spine, total hip, and femoral neck |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject has provided informed consent/assent prior to initiation of any study
specific activities/procedures.
OR
• Subject’s legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent.
• Females who were initially randomized to the romosozumab to ALN sequential
treatment arm of the ARCH study and
- who have completed the Month 36 visit of the ARCH study
- who did not discontinue investigational product during the ARCH study and therein received at least 75% of planned romosozumab and ALN dosing
• Subject meets the following BMD criteria
- Subject has a DXA BMD T-score ≤ -2.0 at the total hip or femoral neck (at or within 4 weeks of the start of screening), as assessed by imaging vendor. |
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E.4 | Principal exclusion criteria |
Disease Related
• Subjects with a positively adjudicated osteonecrosis of the jaw (ONJ) or atypical femoral fracture (AFF) event in the ARCH study or any history of ONJ or AFF events.
• Vitamin D insufficiency (defined as 25 (OH) vitamin D levels < 20 ng/mL as determined by the central laboratory). Vitamin D repletion and retesting within the screening window will be permitted.
• Current, uncontrolled hyper- or hypothyroidism. Uncontrolled hyperthyroidism is defined as thyroid-stimulating hormone (TSH) and thyroxine (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.
Albumin-adjusted serum calcium levels may be retested once in case of an elevated albumin-adjusted serum calcium level within 1.1 x the ULN as assessed by the central laboratory.
• History of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of the results, such as sclerosteosis, Paget’s disease.
Other Medical Conditions
• Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years from the start of this study.
• 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).
• Positive for Hepatitis B.
• Positive for Hepatitis C, Chronic Hepatitis C, and negative viral load while receiving treatment for Hepatitis C.
• Positive results for Human Immunodeficiency Virus (HIV) or known to be HIV-positive
Prior/Concomitant Therapy
• Subjects who have stopped taking ALN for > 3 months since ending the ARCH study and prior to enrollment in this study.
• Use of strontium ranelate, or fluoride (for osteoporosis): more than 1 month of cumulative use within 5 years prior to randomization for, during, or after completion of the ARCH study.
• Use of Intravenous (IV) bisphosphonates.
- Zoledronic acid:
o any dose received within 3 years prior to randomization for, during, or after completion of the ARCH study
o more than 1 dose received within 5 years prior to randomization for, during, or after completion of the ARCH study
- IV ibandronate or IV pamidronate:
o any dose received within 12 months prior to randomization for, during, or after completion of the ARCH study
o more than 3 years of cumulative use, unless last dose received ≥ 5 years prior to randomization for the ARCH study
o Use of oral bisphosphonates:
- any dose received within 3 months prior to randomization for, during, or after completion of the ARCH study
- more than 1 month of cumulative use between 3 and 12 months prior to randomization for, during, or after completion of the ARCH study
- more than 3 years of cumulative use, unless last dose received ≥ 5 years prior to randomization for the ARCH study
• Use of denosumab or any cathepsin K inhibitor, such as odanacatib (MK-0822): any dose received within 18 months prior to randomization for, during, or after completion of the ARCH study.
• Use of teriparatide or any PTH analogs:
- any dose received within 3 months prior to randomization for, during, or after completion of the ARCH study
- more than 1 month of cumulative use between 3 and 12 months prior to randomization for, during, or after completion of the ARCH study
• Use of systemic oral or transdermal estrogen or SERMs: more than 1 month of cumulative use within 6 months prior to randomization for, during, or after completion of the ARCH study.
• Use of hormonal ablation therapy: more than 1 month of cumulative use within 6 months prior to randomization for, during, or after completion of the ARCH study.
• Use of tibolone, cinacalcet, or calcitonin: any dose received within 3 months prior to randomization for, during, or after completion of the ARCH study.
• Systemic glucocorticosteroids: ≥ 5 mg prednisone equivalent per day for more than 14 days within 3 months prior to randomization for, during, or after completion of the ARCH study.
Prior/Concurrent Clinical Study Experience
• 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(ies). Other investigational procedures while participating in this study are excluded. Participation in the ARCH study is exempt from this exclusion criterion.
Please refer to study protocol for complete list. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Percent change from baseline to Month 12 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 to Month 6 and Month 24 in BMD at the lumbar spine
• Percent change from baseline to Months 6, 12, and 24 in BMD at the total hip and femoral neck
• Percent change from baseline to Months 1, 3, 6, and 12 in Procollagen Type 1 N-telopeptide (P1NP) and Type I collagen C-telopeptide (CTX) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Months 1, 3, 6, 12, and 24 |
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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) | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 |
Hong Kong |
Mexico |
Russian Federation |
South Africa |
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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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End of Study (end of trial):
Defined as the date when the last subject is assessed or receives an intervention for evaluation in the study (ie, last subject last visit), following any additional parts in the study (eg, long-term follow-up), as applicable |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 14 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 14 |