E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
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 evaluate a treatment decision algorithm based upon ‘in vivo’ demonstration of TNFα by using a radiolabeled scintigraphic procedure with Technetium-labeled Cimzia®. To demonstrate that Cimzia® has a larger effect than alternative therapies (Orencia®/Roactemra®) in scintigraphy positive patients as compared to scintigraphy negative patients. Thus, we want to show that there is an interaction between the scintigraphic result and the treatment. |
|
E.2.2 | Secondary objectives of the trial |
A secondary objective is to show superiority of Cimzia® in the scintigraphy positive patients. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age between 18 and 70 years with presence of documented diagnosis (clinical evaluation, x-ray hands and feet ≤ 3 months before inclusion) of rheumatoid arthritis (RA) at least 3 months and no longer than 15 years defined according to the ACR/EULAR criteria 2010. • It should be a RA who has an inadequate response to at least 2 DMARDs of which one is methotrexate. Methotrexate should be started at least 3 months before baseline and the dosage and route of administration should be stable for at least 2 months before baseline. The minimal weekly doses allowed for methotrexate is 10 mg and the maximal dose is 25 mg. • Conform with the Belgian reimbursement criteria for anti-TNF therapy, the DAS28 should be > 3.7. • Patients should have failed one, but maximum two anti-TNFα treatments other than Cimzia®. • Active disease according to the rheumatologist with DAS28 score ≥3.7 and at least 1 swollen joint clinically on a 66-swollen joint count.
|
|
E.4 | Principal exclusion criteria |
• The patients may not have received any experimental biological and/or non-biological therapy in the last 3 months or 5 times the half-life of the therapy before baseline. • The patients may not have received a treatment with certolizumab pegol and/or abatacept and/or tocilizumab and/or rituximab. • Known hypersensitivity to certolizumab pegol ,abatacept or tocilizumab or one of its excipients. • Current or recent history of severe progressive uncontrolled renal, hepatic, hematological, gastro-intestinal, endocrinal, pulmonal, cardial, neurological or cerebral disorders. • Severe or life-threatening infection in the last 6 months; signs and symptoms of a current or recent infection. • Actieve tuberculosis. • Latent tuberculosis, with the exception of patient who are adequately treated according to the local regulations. Absence of latent tuberculosis is defined as a negative tuberculine skintest (Mantoux PPD test) and a recent (< 6 months) x-ray of thorax which shown no suggestive injuries for TB. • Known or current viral hepatitis B or hepatitis C infection. Known HIV infection. • Presence of malignity or history of a maligne pathology. • History of lymphoproliferatic disorder or signs or symptoms suggestive for such a disorder. • Moderate to severe cardiac failure (NYHA-class III/IV). • Women of childbearing potential and who are not taking adequate contraception (such as oral/parenteral/implantable hormonal therapy, intra-uterine device, or barrier and spermicide method). Patient should agree to use adequate contraception during the study and until 12 weeks after the last administration of certolizumab pegol, abatacept or tocilizumab.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Demonstration of significant ‘in vivo’ TNFα expression would predict a good response to the ‘TNFα Class Switch’-option, whereas absence of demonstrable TNFα would result in a better response to a biological with another mode of action. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
|
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 | 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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Evaluation of a treatment decision algorithm based upon ‘in vivo’ demonstration of TNFα by using a radiolabeled scintigraphic procedure with Technetium-labeled Cimzia®. |
|
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | 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 | No |
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 | 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
|
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |