E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.
Subjects with decreased Bone Mineral Density (BMD) at risk for hip fractures is the medical condition being investigated.
|
|
E.1.1.1 | Medical condition in easily understood language |
Osteoporosis, skeletal disease characterized with low bone mass |
|
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 | 14.1 |
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 |
|
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 |
Due to the early termination of patient enrollment, all statistical tests will be performed when the sample size permits and the resulting analyses will be more exploratory in nature. The original planned primary, secondary, and exploratory analyses are described below:
The primary objective of this study is to show increased BMD of the proximal femur (total hip BMD) after injection of rhBMP-2/CPM (either 1.0 mg/mL or 2.0 mg/mL) as an adjunct to systemic osteoporosis therapy. To assess the primary objective, BMD will be measured by dual-energy x-ray absorptiometry (DXA) every 3 months from 6 to 12 months. |
|
E.2.2 | Secondary objectives of the trial |
- Assess acute and long-term safety of administering rhBMP 2/CPM in subjects with decreased BMD.
- Assess the feasibility of administering rhBMP-2/CPM as a minimally invasive technique in an outpatient setting.
- Identify a clinically meaningful difference in BMD between rhBMP-2/CPM treatment groups
- Identify number of nonresponders
- Assess changes in BMD relative to femoral neck morphometry, exploring the relation between the femoral neck volume of individual study subjects or groups of subjects, the volume of rhBMP-2/CPM administered, and the overall response to treatment, measured by bone densitometry.
- Evaluate long-term changes in BMD after injection of rhBMP-2/CPM.
- Evaluate bone quality in regions of interest (ROIs), using quantitative volumetric computed tomography.
-Evaluate changes in biochemical markers of bone turnover
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Community-dwelling, ambulatory (with or without assistive device), postmenopausal woman, 65-85 years of age.
[2] BMD T-score (total hip or femoral neck) of -2.5 or less in at least 1 hip. Subjects with BMD T-scores of -2.0 or less may be enrolled if at least 1 of the following risk factors is also present.
[2a] Age ≥75 years
[2b] Maternal (mother) history of fragility fracture
[2c] Subject experienced fragility fracture(s) after age 45
[3] Bilaterally intact proximal femora, without evidence of acute fracture, surgical hardware, or prosthetic implant.
[4] Subjects may either be treatment naive or on a previously established regimen (≥1 year, but <5 years duration) of bisphosphonate therapy (either oral or IV administration is acceptable).
[5] Subjects must be willing to comply with 1 of the 3 protocol-designated oral bisphosphonates (risedronate, alendronate, or ibandronate sodium) with risedronate considered as first-line therapy.
|
|
E.4 | Principal exclusion criteria |
[1] Metabolic bone disorder or disease affecting bone and mineral metabolism (eg, Paget's disease, vitamin D deficiency [<20 ng/mL], hyperparathyroidism, renal osteodystrophy, osteomalacia, hypocalcemia, hypercalcemia)
[2] Previous use of agents that can be considered bone anabolic (eg, PTH, growth hormone, anabolic steroids, or sodium fluoride at bone therapeutic doses)
[3] Previous use of SERMs, HRT, or calcitonin within the past 12 months
[4] Previous use of strontium ranelate
[5] Continuous or intermittent disease that requires systemic glucocorticosteroid treatment in any formulation within the past 6 months (eg, chronic obstructive pulmonary disease, asthma)
[6] Active infection at any anatomical site
[7] History of severe pulmonary or respiratory disorder, such as ARDS, pulmonary stenosis, or right-to-left venoarterial shunt
[8] Evidence of unstable clinically relevant disease (eg, cardiovascular, hepatic, renal, or thyroid disease)
[9] Coagulopathy and/or history of venous thromboembolic events (deep vein thrombosis, pulmonary embolus, retinal vein thrombosis) within the past 12 months , or documented history of prolonged bleeding or spontaneous bruising
[10] BMI >35 kg/m2
[11] Documented history of malignancy, except basal or squamous cell carcinoma that has been treated and fully resolved (ie, cancer free for ≥6 months)
[12] Inflammatory arthritis including rheumatoid, psoriatic, or crystal-induced (gouty) arthritis, or those associated with SLE, spondyloarthropathy, Reiters syndrome, or Crohns disease
[13] Any condition requiring anticonvulsant therapy with an agent that affects 25-OH Vitamin D metabolism
[14] AST, ALT, or total bilirubin ≥1.5 times the ULN at screening
[15] ALP or serum creatinine ≥2 times the ULN at screening
[16] Any of the following contraindications to MRI:
[16a] Pacemaker or implanted defibrillator
[16b] Any metallic implant (eg, clips) unless non-ferromagnetic, such as titanium
[16c] Implanted drug or infusion devices (eg, insulin pump)
[16d] Any electronically, magnetically, or mechanically activated implants
[16e] Neurologic and biostimulators
[16f] Cochlear, otologic, or ear implants and hearing aids
[16h] Implanted medical devices (eg, Swan Ganz catheter)
[16i] Shrapnel or bullets
[16j] History of claustrophobia (unless an open MRI is available for image acquisition)
[16k] Any other MRI contraindication identified by the Investigator or mandated by their institution’s Department of Radiology |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Due to the early termination of patient enrollment, all statistical tests will be performed when the sample size permits and the resulting analyses will be more exploratory in nature. The original planned primary, secondary, and exploratory analyses are described below:
The primary endpoint is change from baseline in BMD at 12 months. Because BMD is directly affected by surface area (BMD=bone mineral content [BMC]/area) and treatment with rhBMP-2/CPM may increase the overall area of the surrounding region by inducing new bone formation, BMC (bone mineral content) may be an important measure of treatment effect. The change from baseline in BMC at 12 months will be included as a secondary endpoint. Also the change from baseline in bone area will be utilized as an exploratory endpoint in order to assess potential differences between BMD and BMC endpoints.
The primary analysis of changes from baseline in BMD between the rhBMP-2/CPM-treated and SOC groups will be based on a two-sample t-test of the 12-month data to test the null hypothesis of no treatment differences between the SOC and each of the rhBMP-2/CPM groups. Data from 12 months of follow-up will be used to test this hypothesis. Additionally, a linear model will test changes in BMD including covariates for baseline BMD, previous osteoporosis therapy (the baseline stratification factor), and the treatment group. The methodology of Galbraith and Marschner will be used which adjusts for missing assessments by using the information from both the 6- and 9- month assessments in the model
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
All subjects will receive systemic osteoporosis therapy consisting of oral biphosponates Ca Vit D |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 |
|
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
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 |