E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid arthritis and osteoporosis |
leddegigt og knogleskørhed |
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E.1.1.1 | Medical condition in easily understood language |
rheumatoid arthritis and osteoporosis |
leddegigt og knogleskørhed |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031289 |
E.1.2 | Term | Osteoporosis, unspecified |
E.1.2 | System Organ Class | 100000004859 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039076 |
E.1.2 | Term | Rheumatoid arthritis and other inflammatory polyarthropathies |
E.1.2 | System Organ Class | 100000004859 |
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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 assess the effect of discontinuation of alendronate on bone metabolism in patients with non-glucocorticoid treated rheumatoid arthritis and alendronate-treated osteoporosis with a current T-score in the range of osteopenia. - to assess the effect of discontinuation of ALN on C-terminal telopeptide crosslinks (CTX) and Type 1 procollagen amino-terminal-propeptide (P1NP) after 6 months - to assess the effect of discontinuation of ALN on BMD at 2 years
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E.2.2 | Secondary objectives of the trial |
- to assess the effect of discontinuation of ALN on vBMD at 2 years - to assess the effect of discontinuation of ALN on other biochemical markers of bone metabolism after 6, 12 and 24 months - to evaluate and compare the changes in vBMD in cancellous and cortical bone respectively, after discontinuation of ALN - to evaluate the correlation between RA activity and bone metabolism
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients (> 18 years) with rheumatoid arthritis according to the ACR/EULAR (2010) classification criteria (10) - patients must have been treated with oral bisphosphonatesalendronate for 5 years or longer, the last three years with alendronate - current T-score on DXA better than or equal to -2,5 (femoral) and -3,0 (vertebral) - receiving treatment on an outpatient basis - negative pregnancy test (serum HCG) prior to trial start and the use of contraception throughout the study period and for 1 month after conclusion of the study period for women of childbearing potential. Plasma T1/2 of ALN is less than 2 hours. The forms of contraception include: intrauterine device (IUD) and hormonal anticontraceptives (contraceptive pill, implant, patch or injection or vaginal ring). Sterile and non-fertile participants do not have to use contraception. Sterile or non-fertile is defined as having undergone surgical sterilization (vasectomy / bitalteral tubectomy, hysterectomy and bilateral ooferectomy) or post-menopausal status, defined as absence of menstrual period for at least 12 months prior to enrollment. Postmenopause will be confirmed by measurement of s-FSH prior to enrollment. - ability and willingness to give written informed consent and to meet the requirements of the trial protocol.
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E.4 | Principal exclusion criteria |
- history of hip fracture due to osteoporosis - - history of vertebral fragility fractures within the last three years OR fragility fractures in more than two vertebrae - - history of non-vertebral fragility fractures (fingers and toes not included) within the last three years - osteonecrosis of the jaw. - history of or ongoing systemic GC treatment within the last 6 months (intraarticular injections are approved) - known allergy toward any components of the study medicine - prior or ongoing treatment with with BPs other than ALN or other antiosteoporosis drugs such as hormone replacement therapy (HRT) or teriparatide (low-dose HRT up to 1mg/day is accepted) - evidence of active malignant disease - metabolic bone disease other than osteoporosis - hypo- or hyperthyroidism - hypocalcaemia - impaired renal function (eGFR <35ml/min) - known disease of the esophagus that might impair the ability to swallow the tablets such as achalasia, dysphagia or strictures - history of upper gastrointestinal disease within 1 year prior to enrollment such as peptic ulcer, upper GI bleeding, gastritis, duodenitis or surgical procedures to the upper GI-tract - allergy towards any of the substances in the study medicine
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E.5 End points |
E.5.1 | Primary end point(s) |
a) changes in serum CTX and P1NP from baseline 6 months b) changes in BMD from baseline to 2 years follow-up on DXA on left hip and spine ( vertebrae L2-L3)
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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) |
c) changes in vBMD from baseline to 2 years follow-up on HR-pQCT after 1 and 2 years in metacarpals 2-4 and at the distal radius d) changes from baseline to 6, 12 and 24 months in the following serological markers of bone metabolism and inflammation : - CTX - P1NP - Bone-specific alkaline phosphatase, (bsAP) - Tumor necrosis factor-alfa (TNF), - RANK-Ligand (RANK-L) - Osteoprotegrin (OPG) - Osteocalcin - Sclerostin,(SCL) - Interleukins, 6 and 17, (IL-6, IL-17) - C-reactive protein (CRP) e) changes in vBMD in cancellous and trabecular bone respectively from baseline to 2 years f) mean DAS-28-CRP throughout the study period (24 months) g) new erosions on X-ray according to the Sharp-van-der-Heijde-score
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
c)months 12 and 24 d)months 6, 12 and 24 e)month 24 f)month 24 g)month 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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
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 | 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) | 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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |