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 |
Rheumatoid arthritis (RA) in adults. RA is a long-term disease that leads to inflammation of the joints and surrounding tissues. It can also affect
other organs. |
|
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 | 14.1 |
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 |
|
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 |
• The efficacy of treatment with 162 mg tocilizumab (TCZ) given subcutaneously (SC) weekly
versus 8 mg/kg TCZ given intravenously (IV) every 4 weeks with regard to noninferiority of the proportion of patients who achieve ACR20 at Week 24.
• The safety of treatment with 162 mg TCZ given SC weekly versus 8 mg/kg TCZ
given IV every 4 weeks, with regard to AEs and laboratory assessments. |
|
E.2.2 | Secondary objectives of the trial |
• Long-term safety and efficacy
• PK and PD of TCZ following SC administration
• Immunogenicity of TCZ following SC administration
• Effect of IV to SC switch on the safety, efficacy, PK and PD of TCZ |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
An optional sub-study will be performed with consented patients as follows:
PK-PD Sub-Study in the Double-Blind Study Period:
- to determine PK and PD (sIL-6R and IL-6) following TCZ SC administration, in the 24-week double-blind period |
|
E.3 | Principal inclusion criteria |
Adult patients >= 18 years
Rheumatoid arthritis of >= 6 months duration
Swollen joint count (SJC) ≥ 4 (66 joint count), and tender joint count (TJC) ≥ 4 (68 joint count) both at screening and baseline visits
At screening, CRP ≥ 10 mg/L (≥1 mg/dL) and/or ESR ≥28 mm/h
Have to be on at least one permitted DMARD, which has been at a stable dose for at least 8 weeks prior to baseline
|
|
E.4 | Principal exclusion criteria |
Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomisation
Prior history of or current inflammatory joint disease other than RA
Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20.
Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
Active current infection or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds).
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the proportion of patients achieving an ACR 20 response at Week 24. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Proportion of patients with an ACR50 response at Week 24
2. Proportion of patients with an ACR70 response at Week 24
3. Proportion of patients with a DAS28 < 2.6 (DAS remission) at Week 24
4. Proportion of patients achieving a decrease of ≥0.3 in HAQ-DI from baseline to Week 24
5. Proportion of patients who withdrew due to lack of therapeutic
response at Week 24 |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
exploratory biomarkers (DNA and non-DNA); immunogenicity assessments |
|
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 75 |
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 | No |
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 |
Argentina |
Australia |
Brazil |
Bulgaria |
Canada |
Colombia |
France |
Germany |
Guatemala |
Hong Kong |
Italy |
Lithuania |
Mexico |
New Zealand |
Peru |
Philippines |
Poland |
Romania |
Russian Federation |
Singapore |
South Africa |
Spain |
Thailand |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The end of the study will occur when the last participating patient completes the last
scheduled visit or when the sponsor decides to discontinue the study or evelopment
program. |
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |