Safety and efficacy of tocilizumab in combination with placebo compared with tocilizumab in combination with methotrexate, with possible addition of other disease-modifying antirheumatic drugs (DMARDs), in patients with moderate to severe active rheumatoid arthritis who are not responding adequately to their current therapy with methotrexate.

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2008-001847-20-GB
• Date of registration: 09/09/2008
• Prospective Registration: Yes
• Primary sponsor: F Hoffmann-La Roche Ltd.
• Public title: Safety and efficacy of tocilizumab in combination with placebo compared with tocilizumab in combination with methotrexate, with possible addition of other disease-modifying antirheumatic drugs (DMARDs), in patients with moderate to severe active rheumatoid arthritis who are not responding adequately to their current therapy with methotrexate.
• Scientific title: Randomized placebo-controlled study to evaluate the safety and efficacy of adding tocilizumab (TCZ) to methotrexate (MTX) versus switching to TCZ (placebo controlled), with possible addition of other disease-modifying anti-rheumatic drugs (DMARDs), in patients with active rheumatoid arthritis who have inadequately responded to prior MTX treatment. - ACT RAY
• Date of first enrolment: 19/12/2008
• Target sample size: 470
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-001847-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: this study is placebo controlled for MTX and open label for TCZ; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Brazil, Croatia, Denmark, Estonia, France, Germany, Greece, Israel, Italy, Latvia, Netherlands, Norway, Romania, Russian Federation, Serbia, Spain, Sweden, Thailand, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
•adult patients, >= 18 years of age;
•moderate to severe active rheumatoid arthritis (DAS28 >4.4);
•inadequate response to methotrexate;
•on a stable dose of >= 15mg/week methotrexate for at least 6 weeks.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 450
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 106

Exclusion criteria:
•prior treatment with a biologic;
•RA functional class IV;
•known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections;
•evidence of active malignant disease.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: RoActemra®
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: tocilizumab
CAS Number: 375823-41-9
Current Sponsor code: RO4877533
Other descriptive name: IL-6 receptor inhibitor, recombinant humanized monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: Methotrexate 'Lederle' 2.5mg Tablets
Product Name: Methotrexate 'Lederle' 2.5mg Tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: Methotrexate Disodium
CAS Number: 7413345
Other descriptive name: Methotrexate as methotrexate disodium
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): •DAS28 remission rate (RR) at week 24. DAS28 remission is defined as DAS28 < 2.6.

Secondary Objective: To compare the effect of TCZ plus MTX versus TCZ plus PBO on progression of structural damage at week 52 in MTX inadequate responders with moderate to severe active RA who may receive a DMARD in addition to TCZ and MTX/PBO after week 24.

To compare the safety of TCZ plus MTX versus TCZ plus PBO with regard to AEs and laboratory assessments in MTX inadequate responders with moderate to severe active RA who may receive a DMARD in addition to TCZ and MTX/PBO after week 24.

To assess clinical and radiographic efficacy over 2 years (including earlier time points) of treatment with TCZ plus MTX versus TCZ plus PBO as assessed by measures including clinical disease activity, x-rays and quality of life and functional scales.

To assess the course of disease activity as well as treatment efficacy and safety in patients for the duration of 52 weeks after discontinuation of TCZ because of remission.

Main Objective: To compare the effect of TCZ in combination with MTX versus TCZ alone (i.e. receiving placebo matching MTX) on DAS28 remission at week 24 in MTX inadequate responders with moderate to severe active RA.

Timepoint(s) of evaluation of this end point: week 24

Secondary Outcome(s)

Secondary end point(s): Inhibition of progressive joint damage [Time Frame: Week 52]
ACR20/50/70/90 response, and time to response [Time Frame: Throughout study ]
DAS, DAS28, HAQ [Time Frame: Throughout study ]

Timepoint(s) of evaluation of this end point: week 52 / throughout the study

Secondary ID(s)

2008-001847-20-ES

MA21488

NCT00810199

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 29/05/2015
• Date Completed: 10/01/2013
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-001847-20/results