Rheumatoid ArthritisPhase 4NCT01399697
A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate Versus RoActemra/Actemra Monotherapy in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate
A Phase 4 study testing methotrexate and tocilizumab [RoActemra/Actemra] in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 54 sites in Spain.
Trial summary
This randomized, double-blind, parallel-group study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in combination with methotrexate versus RoActemra/Actemra monotherapy in patients with rheumatoid arthritis and an inadequate response to methotrexate. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- methotrexate and tocilizumab [RoActemra/Actemra]
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 261 participants
- Where
- 54 sitesSpain
- Study dates
- Sep 2011to May 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients, >/= 18 years of age
- Active moderate to severe rheumatoid arthritis (DAS28 >/= 3.2) at baseline
- Currently receiving methotrexate for at least 12 weeks, at a stable oral dose of at least 15 mg/week for at least 6 weeks prior to treatment (Day 1)
- Body weight < 150 kg
- Oral corticoids must have been at stable dose for at least 25 out of 28 days prior to baseline; maximum dose 10 mg/day
Who cannot join
- Pregnant or nursing women
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after baseline
- Rheumatic autoimmune disease other than RA
- Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis
- Prior history of or current inflammatory joint disease other than RA
- Treatment with a biologic agent at any time prior to baseline
Show all 14Show fewer
- Treatment with traditional DMARDs other than methotrexate within 1 month (for leflunomide 3 months) prior to baseline
- Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
- Previous treatment with RoActemra/Actemra
- History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
- Known active current or history of recurrent infection
- History of or currently active primary or secondary immunodeficiency
- Active tuberculosis requiring treatment within the previous 3 years
- Positive for HIV infection
Trial locations and contacts
54 sites in 1 country.
54 sites in 1 country
Spain54 sites
Study site
A Coruña, La Coruña, 15006
Study site
Albacete, Albacete, 02006
Study site
Alcalá de Henares, Madrid, 28805
Study site
Badajoz, Badajoz, 06080
Study site
Badalona, Barcelona, 08915
Study site
Barakaldo, Vizcaya, 48903
Study site
Barcelona, Barcelona, 08003
Study site
Barcelona, Barcelona, 08025
Study site
Barcelona, Barcelona, 08035
Study site
Barcelona, Barcelona, 08036
Study site
Barcelona, Barcelona, 08907
Study site
Bilbao, Vizcaya, 48013
Study site
Cáceres, Caceres, 10310
Study site
Cadiz, Cadiz, 11009
Study site
Cartagena, Murcia, 30203
Study site
Córdoba, Cordoba, 14004
Study site
El Palmar, Murcia, 30120
Study site
Fuenlabrada, Madrid, 28942
Study site
Galdakao, Vizcaya, 48960
Study site
Granada, Granada, 18003
Study site
Granada, Granada, 18014
Study site
Granollers, Barcelona, 08402
Study site
Guadalajara, Guadalajara, 19002
Study site
Las Palmas de Gran Canaria, Las Palmas, 35020
Study site
León, Leon, 24071
Study site
Lugo, Lugo, 27004
Study site
Madrid, Madrid, 28007
Study site
Madrid, Madrid, 28031
Study site
Madrid, Madrid, 28034
Study site
Madrid, Madrid, 28040
Study site
Madrid, Madrid, 28041
Study site
Madrid, Madrid, 28046
Study site
Madrid, Madrid, 28905
Study site
Málaga, Malaga, 29009
Study site
Manises, Valencia, 46940
Study site
Menorca, Balearic Islands, 07701
Study site
Mérida, Badajoz, 06800
Study site
Orihuela, Alicante, 03314
Study site
Salamanca, Salamanca, 37007
Study site
Santa Cruz de Tenerife, Tenerife, 38010
Study site
Santiago de Compostela, La Coruña, 15706
Study site
Seville, Sevilla, 41009
Study site
Seville, Sevilla, 41013
Study site
Terrassa, Barcelona, 08221
Study site
Toledo, Toledo, 45004
Study site
Torrelavega, Cantabria, 39300
Study site
Torrevieja, Alicante, 03186
Study site
Valdemoro, Madrid, 28342
Study site
Valencia, Valencia, 46010
Study site
Valencia, Valencia, 46017
Study site
Valenica, Valencia, 46009
Study site
Vigo, Pontevedra, 36214
Study site
Villajoyosa, Alicante, 03570
Study site
Villarreal, Castellon, 12540
About this study
Official title: A Multi-center Study of the Safety and Effect on Disease Activity of Tocilizumab (TCZ) in Combination With MTX Versus Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis, With Inadequate Response to MTX (Defined as DAS 28 > 3,2)
This randomized, double-blind, parallel-group study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in combination with methotrexate versus RoActemra/Actemra monotherapy in patients with rheumatoid arthritis and an inadequate response to methotrexate. All patients will receive RoActemra/Actemra 8 mg/kg intravenously (iv) every 4 weeks plus oral methotrexate for 16 weeks. Patients achieving low disease activity at Week 16 will be randomized to receive a further 12 weeks of RoActemra/Actemra treatment plus either methotrexate or placebo. Anticipated time on study treatment is 28 weeks.
- Conditions
- Rheumatoid Arthritis
- Being tested
- methotrexate, placebo, tocilizumab [RoActemra/Actemra]
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methotrexateDrug
orally, Week 1 - 16
methotrexateDrug
orally, Week 17-28
placeboDrug
methotrexate placebo orally, Week 17-28
tocilizumab [RoActemra/Actemra]Drug
8 mg/kg iv every 4 weeks, 28 weeks
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Not described Receives: Drug: methotrexate; Drug: tocilizumab [RoActemra/Actemra] |
| B | Active comparator | Not described Receives: Drug: methotrexate; Drug: placebo; Drug: tocilizumab [RoActemra/Actemra] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Disease Activity Score Based on 28-Joint Count (DAS28) From Week 16 to Week 28
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]), and general health status (participant global assessment of disease activity using visual analog scale [VAS], range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Measured: Baseline, Week 16, and Week 28
Secondary outcomes (8)
Percentage of Participants With DAS28 Score Less Than (<) 2.6 at Week 28
The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores indicate worsening. DAS28 <2.6 equals (=) remission.
Measured: Week 28
Percentage of Participants With Clinical Disease Activity Index (CDAI) <2.8 at Week 28
CDAI is the sum of tender and swollen joint count based on 28 joints and the participant and physician global disease assessment (VAS 0-10 centimeters [cm]). CDAI total score 0-76; higher scores = greater affect due to disease activity. CDAI <2.8 = clinical remission.
Measured: Week 28
Percentage of Participants With Simplified Disease Activity Index (SDAI) <3.3 at Week 28
SDAI is calculated by a simple numerical sum of tender and swollen joint count (based on a 28-joint assessment), participant and physician global assessment of disease activity (VAS 0-10 cm), and level of C-reactive protein in milligram per deciliter (mg/dL). SDAI total score 0-86; higher scores = greater affect due to disease activity. SDAI <3.3 = clinical remission.
Measured: 28 weeks
Change in the Health Assessment Questionnaire Disability Index (HAQ-DI) From Week 16 to Week 28
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Measured: Week 16 and Week 28
Change in the Quality of Life Questionnaire (Short Form-12 [SF-12]) From Week 16 to Week 28 in Mental Health
Quality of life questionnaire (SF-12) scores were computed using the scores of 12 questions and ranged from 0 to 100, where a 0 score indicated the lowest level of health measured by the scales and 100 indicated the highest level of health. A negative change from baseline indicated decline in health and higher scores indicated improvement in health.
Measured: Week 16 and Week 28
Change in the Quality of Life Questionnaire (SF-12) From Week 16 to Week 28 in Physical Health
Quality of life questionnaire (SF-12) scores were computed using the scores of 12 questions and ranged from 0 to 100, where a 0 score indicated the lowest level of health measured by the scales and 100 indicated the highest level of health. A negative change from baseline indicated a worsening of quality of life.
Measured: Week 16 and Week 28
Change From Week 16 to Week 28 in Global Assessment of Disease Activity as Assessed With the Visual Analogue Scale (VAS) Performed by Participant
Participants were asked to rate their global assessment of disease activity on a scale ranging from 0=very good to 100=very bad. The scale was represented by a line with 0 at the left edge and 100 at the right edge. The participant was asked to mark the line corresponding to the assessment of their disease activity. The distance from the left edge was measured in mm.
Measured: Week 16 and Week 28
Change From Week 16 to Week 28 in Global Assessment of Disease Activity Assessed Using the VAS Performed by the Investigator
Participants were asked to rate their global assessment of disease activity on a scale ranging from 0=very good to 100=very bad. The scale was represented by a line with 0 at the left edge and 100 at the right edge. The participant was asked to mark the line corresponding to the assessment of their disease activity. The distance from the left edge was measured in mm.
Measured: Week 16 and Week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2011 (estimated)
- Study startSep 2011
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 261 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01399697
- Sponsor's protocol ID
- ML27828
- Status last verified
- May 2015
- First submitted
- 20 Jul 2011
- Last updated
- 13 Jul 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center Study of the Safety and Effect on Disease Activity of Tocilizumab (TCZ) in Combination With MTX Versus Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis, With Inadequate Response to MTX (Defined as DAS 28 > 3,2)
- ClinicalTrials.gov ID
- NCT01399697
- Acronym / sponsor ID
- ML27828
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 261 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Sep 2011
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 22 Jul 2011 (estimated)
- Results
- Posted 13 Jul 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized, double-blind, parallel-group study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in combination with methotrexate versus RoActemra/Actemra monotherapy in patients with rheumatoid arthritis and an inadequate response to methotrexate. All patients will receive RoActemra/Actemra 8 mg/kg intravenously (iv) every 4 weeks plus oral methotrexate for 16 weeks. Patients achieving low disease activity at Week 16 will be randomized to receive a further 12 weeks of RoActemra/Actemra treatment plus either methotrexate or placebo. Anticipated time on study treatment is 28 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: methotrexate, Drug: tocilizumab [RoActemra/Actemra] |
| B | Active comparator | Drug: methotrexate, Drug: placebo, Drug: tocilizumab [RoActemra/Actemra] |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients, >/= 18 years of age
- Active moderate to severe rheumatoid arthritis (DAS28 >/= 3.2) at baseline
- Currently receiving methotrexate for at least 12 weeks, at a stable oral dose of at least 15 mg/week for at least 6 weeks prior to treatment (Day 1)
- Body weight < 150 kg
- Oral corticoids must have been at stable dose for at least 25 out of 28 days prior to baseline; maximum dose 10 mg/day
Key exclusion criteria (14 listed)
- Pregnant or nursing women
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after baseline
- Rheumatic autoimmune disease other than RA
- Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis
- Prior history of or current inflammatory joint disease other than RA
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| methotrexateorally, Week 1 - 16 | Drug | A, B |
| methotrexateorally, Week 17-28 | Drug | A |
| placebomethotrexate placebo orally, Week 17-28 | Drug | B |
| tocilizumab [RoActemra/Actemra]8 mg/kg iv every 4 weeks, 28 weeks | Drug | A, B |
Primary outcome
Change in Disease Activity Score Based on 28-Joint Count (DAS28) From Week 16 to Week 28
Time frame: Baseline, Week 16, and Week 28
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]), and general health status (participant global assessment of disease activity using visual analog scale [VAS], range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
8 secondary outcomes
Percentage of Participants With DAS28 Score Less Than (<) 2.6 at Week 28
Time frame: Week 28
Percentage of Participants With Clinical Disease Activity Index (CDAI) <2.8 at Week 28
Time frame: Week 28
Percentage of Participants With Simplified Disease Activity Index (SDAI) <3.3 at Week 28
Time frame: 28 weeks
Change in the Health Assessment Questionnaire Disability Index (HAQ-DI) From Week 16 to Week 28
Time frame: Week 16 and Week 28
Change in the Quality of Life Questionnaire (Short Form-12 [SF-12]) From Week 16 to Week 28 in Mental Health
Time frame: Week 16 and Week 28
Change in the Quality of Life Questionnaire (SF-12) From Week 16 to Week 28 in Physical Health
Time frame: Week 16 and Week 28
Change From Week 16 to Week 28 in Global Assessment of Disease Activity as Assessed With the Visual Analogue Scale (VAS) Performed by Participant
Time frame: Week 16 and Week 28
Change From Week 16 to Week 28 in Global Assessment of Disease Activity Assessed Using the VAS Performed by the Investigator
Time frame: Week 16 and Week 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Rheumatoid Arthritis
RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
54 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing methotrexate and tocilizumab [RoActemra/Actemra] in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 54 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 54 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Disease Activity Score Based on 28-Joint Count (DAS28) From Week 16 to Week 28 (time frame: Baseline, Week 16, and Week 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2015.