E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This is an exploratory sub-study of Protocol 018 (Eudract N°2007-002693-66) to identify biomarkers of physical function. This biomarker sub-study will use an ongoing clinical study (Protocol 018) for osteoporosis as a starting point for identification of molecular biomarkers in circulating blood for patient identification and sarcopenia progression. Patients recruited in Protocol 018 are women 65 years of age or older with osteoporosis and either 0 or 1 prior vertebral fracture. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031283 |
E.1.2 | Term | Osteoporosis fracture |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
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 |
(1A) To evaluate the phenotypic distribution of aLBM, SPPB, and gait speed in the study population. Specifically to determine if, at baseline, measured traits (aLBM, SPPB and/or gait speed) form an appropriate distribution.
(1B) To identify biomarkers of sarcopenia by evaluating low aLBM, low SPPB, and low gait speed, separately and in combination, by examining DNA and RNA in circulating blood.
(2A) To determine if there is a measurable change in aLBM, SPPB, and gait speed over time within the duration of the study. Specifically to determine if the rate-of-change in the measured traits (aLBM, SPPB and/or gait speed) form an appropriate distribution.
(2B) To identify biomarkers of rate-of-change (fast vs slow) of aLBM, SPPB, and gait speed, separately or in combination, by examining DNA and RNA in circulating blood. |
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E.2.2 | Secondary objectives of the trial |
Exploratory Objectives:
(1) To perform multiple and partial correlation analyses to estimate the relationship among the following variables: longitudinal changes in appendicular lean body mass, measured by total body DXA, longitudinal changes in the SPPB score, longitudinal changes in gait speed, and longitudinal changes in the chair stand test.
(2) To estimate the relationship between baseline incident mobility-disability (defined as self-reported difficulty with either walking 400 meters or climbing 10 steps without resting) and baseline (a) aLBM; (b) SPPB score; (c) gait speed.
(3) To estimate the relationship between incident mobility-disability in years 2-4 (defined as new-onset of self-reported difficulty with either walking 400 meters or climbing 10 steps without resting) and decline in (a) aLBM; (b) SPPB score; (c) gait speed from baseline to 1 year. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is randomized and actively participating (on treatment) in Protocol 018. If the patient is discontinued from Protocol 018 then she can no longer participate in this sub-study.
2. Patient is willing to participate in the sub-study as indicated by signing the informed consent form for this sub-study. The consent form for this sub-study includes general consent and consent for genetics and RNA testing. |
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E.4 | Principal exclusion criteria |
1. Active conditions that limit general physical strength and function, particularly musculoskeletal in the lower extremities, such as:
• Rheumatoid arthritis, polymyalgia rheumatica, polymyositis, Cushing’s syndrome • Neuromuscular diseases (i.e. stroke, multiple sclerosis) • Major surgery in the lower extremities in the past 2 months
2. Patient has New York Heart Association (NYHA) Class III or IV congestive heart failure
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E.5 End points |
E.5.1 | Primary end point(s) |
Normalized clinical endpoint measurements, such as aLBM changes from baseline, will be directly correlated with mRNA expression levels in an effort to identify gene signatures whose regulations are associated with slow and fast progression of sarcopenia, thus discriminating patients who progress slowly from patients who progress fast with assumption that these clinical endpoint measurements would have two discernible distributions. Since no criteria have yet been established for defining the 'fast' and 'slow', an iterative partial least discriminant analysis developed by the Sponsor will be applied to selected clinical endpoint and mRNA expression data by randomly dividing the data into training and testing sets with a series of pre-defined cutoffs on selected clinical endpoint measurements. Data specific optimal cutoffs for this study will be determined by minimizing the prediction error and balancing between sensitivity and specificity. Pearson correlation coefficients will be calculated for each gene and signatures will then be ranked according to significance of correlations and absolute correlation coefficients. With total of 800 or more samples, it is estimated that the magnitude of correlation needs to be ≥ 0.6 to reach a FDR of 10% for 100 signature genes while testing among 10,000 pre-filtered genes. |
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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 | No |
E.6.5 | Efficacy | No |
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 | Yes |
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 | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 | 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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The exact timepoint for the final visit (i.e. end of study) depends on the accumulation of a sufficient number of fracture events in Protocol 018. It is anticipated that Protocol 018 will end ~3 years after the end of enrollment. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |