E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult Rheumatoid Arthritis |
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E.1.1.1 | Medical condition in easily understood language |
Adult Rheumatoid Arthritis |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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 |
Incidence of infusion reactions |
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E.2.2 | Secondary objectives of the trial |
• To assess the incidence of discontinuations of TCZ due to AE and due to other causes.
• To assess the incidence of increase in ALT, AST and lipids
• To assess the number and % of patients achieving clinical remission (DAS28 < 2.6), LDA after 24 weeks.
• To assess the number and % of patients achieving ACR20, ACR50, ACR70 and ACR90 after 24 weeks
• To assess increase in HAQ after 24 weeks
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or non-pregnant, non-nursing female
2. ≥ 18 years of age
3. Receiving treatment on an outpatient basis
4. RA of ≥ 6 months duration
5. Moderate to severe active RA: (DAS28 ≥ 3.2)
6. Patients on ≥ 1 non-biologic DMARDs and/or TNF-inhibitor at a stable dose for a period ≥ 8 weeks prior to treatment
7. Patients with inadequate clinical response to a stable dose of non-biologic DMARD or anti-TNF therapy
8. If patients are receiving an oral corticosteroid, the dose must have been stable for at least 25 out of 28 days prior to treatment
9. Able and willing to give written informed consent and comply with the requirements of the study protocol
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E.4 | Principal exclusion criteria |
1. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization
2. Rheumatic autoimmune disease other than rheumatoid arthritis
3. Functional class IV as defined by the ACR Classification of Functional Status in
4. Prior history of or current inflammatory joint disease other than RA
Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational agent, whichever is longer) before screening
5. Previous treatment with rituximab and abatacept
6. Pregnant women or nursing (breastfeeding) mothers
7. Females of child-bearing potential who are not using a reliable means of contraception, e.g. physical barrier (patient and partner), contraceptive pill or patch, spermicide and barrier, or IUD
8. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
9. Preivious treatment with any cell-depleting therapy
10. Preivious treatment with any tocilizumab
11. History of or currently active primary or secondary immunodeficiency
12. Known active current og history of recurrent infection (incliding TB)
13. Body weight of > 150 kg
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E.5 End points |
E.5.1 | Primary end point(s) |
Infusion reactions as defined for the pivotale phase III trials. Infusion reactions are defined as any reaction that occurs during the infusion of tocilizumab or during the first 24 hours after the infusion. |
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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) |
Safety
o The number and percentage of patients, where the administration of tocilizumab was stopped due to adverse events and serious adverse events.
o The number and percentage of patients, where the administration of tocilizumab was stopped for other reasons.
o The number and percentage of patients with increased levels of ALT or AST > 1.5 ULN, > 3 ULN and > 5 ULN at any visits.
o The number and percentage of patients with elevated levels of lipids, according to the guidelines for ATP III at any visits.
Efficacy
o The number and percentage of patients who achieved a significant clinical improvement in disease activity score 28, DAS28 (reductions of at least 1,2 units) per visit.
o The number and percentage of patients who achieved low disease activity (DAS28 < 3,2) per visit.
o The number and percentage of patients who achieved DAS28 remission (DAS28 < 2,6) per visit.
o Average (or median) and SD (or quartiles) for DAS28 per visit.
o The number and percentage of patients who achieved ACR20, ACR50, ACR70 and ACR90 at any visit.
o Average (or median) and SD (or quartiles) for hsCRP per visit.
o Average (or median) and SD (or quartiles) of HAQ per visit.
o The number and percentage of patients who achieved a significant clinical HAQ-response, defined as an improvement of at least 0,22 units compared to baseline on HAQ-scale per visit.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety and efficacy evaluations will be done at every visit
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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) | 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 |
Normal infusion time of 1 hour |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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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The end of the study will occur when the last patient, last visit occurs(LPLV). The LPLV is either the date of the last patient to complete the study, or the date at which the last data point from the last patient, which is required for statisitcal analysis, is received, whichever is the later date. |
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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 | 1 |
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 | 1 |
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 |