E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Polymyalgia rheumatica |
Spierreuma |
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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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036099 |
E.1.2 | Term | Polymyalgia rheumatica |
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 study the efficacy of RTX 1*1000mg, with possibility of retreatment between 24-52 weeks, compared to placebo on achieving GC free remission after 52 weeks in relapsing PMR patients during accelerated GC tapering. |
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E.2.2 | Secondary objectives of the trial |
Secondary study parameters include between group difference in proportion of patients in GC-free remission at week 21, the proportion of patients with low dose GC (≤5mg/day) remission at week 21 and 52, difference in PMR-AS, the number of disease relapses/recurrences at week 52, time to GC-free remission and to relapse, GC cumulative dose during the trial, and the proportion of patients with RTX/PCB retreatment, sex differences in frequencies of GC-remission and safety, change in Patient Reported Outcomes (PROMs) , the frequency and types of GC- and RTX-related AE, change in the modified Glucocorticoid Toxicity Index (GTI) and cost-effectiveness. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• A clinical diagnoses of PMR according to the 2012 EULAR/ACR classification criteria. • Re-emerging PMR symptoms and elevated ESR of CRP levels. • Glucocorticoid dose equivalent of prednisolone ≥ 5mg/day.
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E.4 | Principal exclusion criteria |
• Treatment with systemic immunosuppressants (other than GC) 3 months prior to inclusion • (clinical) suspect concomitant giant cell arteritis or other rheumatic inflammatory disease • Concomitant conditions that might significantly interfere with evaluation of PMR pain or movement as judged by the investigator • Previous hypersensitivity for RTX of contra-indications to RTX • Not being able to speak, read or write Dutch
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of relapsing PMR patients in GC-free remission after 52 weeks. |
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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) |
Between group differences in: • Proportion of patients in GC free remission at week 21 • Proportion of patients with low dose GC (≤5mg/day) remission at week 21 and 52 • PMR-AS at each visit • The number of disease relapses/recurrences up to week 52 • The proportion of patients with a disease relapse/recurrence at week 52 • The time from baseline to GC free remission and to relapse • GC cumulative dose at 52 weeks. • Proportion of patients with RTX/PCB retreatment • Proportion of patients who start methotrexate or leflunomide. • Sex differences in frequencies of GC-remission and adverse events. • Changes in patient reported outcomes, concerning pain, fatigue, stiffness and physical function (as recommended by the OMERACT). • Medical consumption and productivity loss • (Changes in) modified glucocorticoid toxicity index (which excludes bone mineral density scan to improve feasibility). • Frequency, types, proportion of patients with, and total numbers of ( especially GC- and RTX-related) AE during the 52 week study. |
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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 | Yes |
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 | 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.8.2.4 | 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 | 6 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |