Rheumatoid ArthritisPhase 3NCT00773461
A Study of Tocilizumab in Combination With DMARD Therapy in Patients With Active Rheumatoid Arthritis.
A Phase 3 study testing tocilizumab [RoActemra/Actemra] in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 9 sites in China.
Trial summary
This 2 arm study will compare the safety and efficacy, with regard to reduction of signs and symptoms, of tocilizumab versus placebo, both in combination with DMARDs, in patients with active rheumatoid arthritis who currently have an inadequate response to DMARD therapy. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- tocilizumab [RoActemra/Actemra]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 209 participants
- Where
- 9 sitesChina
- Study dates
- 31 Oct 2008to 22 Jul 2010
- Phase
- Phase 3
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult patients, 18-70 years of age;
- rheumatoid arthritis for >= 6 months;
- receiving permitted DMARDs, at a stable dose, for >= 8 weeks prior to baseline;
- current inadequate clinical response to DMARDs.
Who cannot join
- major surgery, including joint surgery, within 8 weeks before entering study, or planned major surgery within 6 months following randomization;
- rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis;
- unsuccessful treatment with an anti-TNF agent;
- previous treatment with tocilizumab.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
China9 sites
Peking University People's Hospital
Beijing, 100044
Beijing Union Hospital
Beijing, 100730
General Hospital of Chinese PLA; Department of Hematology
Beijing, 100853
The Third Affiliated Hospital of Sun Yat-Sen University
Guangzhou, 510630
The 1st Affiliated Hospital of Harbin Medical University
Harbin, 150001
Qilu Hospital of Shandong University
Jinan, 250012
Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, 200127
Changhai Hospital of Shanghai
Shanghai, 200433
The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)
Xi'an, 710032
About this study
Official title: A Randomized, Double Blind Study of Safety and Reduction in Signs and Symptoms During Treatment With Tocilizumab Versus Placebo, in Combination With DMARD Therapy, in Patients With Active Rheumatoid Arthritis and Inadequate Response to Current DMARD Therapy
This 2 arm study will compare the safety and efficacy, with regard to reduction of signs and symptoms, of tocilizumab versus placebo, both in combination with DMARDs, in patients with active rheumatoid arthritis who currently have an inadequate response to DMARD therapy. Patients will be randomized 2:1 to receive tocilizumab 8mg/kg iv or placebo iv every 4 weeks, in conjunction with stable DMARD therapy. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
- Conditions
- Rheumatoid Arthritis
- Being tested
- tocilizumab [RoActemra/Actemra], Placebo
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tocilizumab [RoActemra/Actemra]Drug
8mg/kg iv every 4 weeks for 24 weeks
PlaceboDrug
iv every 4 weeks for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: tocilizumab [RoActemra/Actemra] |
| 2 | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24
To achieve an ACR20 response required at least a 20% improvement, compared with baseline, in both (tender joints count)TJC and (swollen joints count) SJC, as well as in 3 out of 5 additional ACR core set variables: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain, health assessment questionnaire disease index (HAQ-DI) and C-reactive protein (CRP). CRP was used primarily for the calculation of the ACR response; if missing, Erythrocyte Sedimentation Rate (ESR) was substituted. ITT sensitivity analysis was carried out using an alternative imputation method (last observation carried forward [LOCF]).
Measured: Week 24
Secondary outcomes (16)
Percentage of Participants With ACR50 and ACR70 Responses at Week 24
To achieve an ACR50 or ACR 70 response required at least a 50% or 70% improvement, compared with baseline in both TJC and SJC, as well as in 3 out of 5 additional ACR core set variables: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain, HAQ-DI and CRP. CRP was used primarily for the calculation of the ACR response; if missing, ESR was substituted.
Measured: Week 24
Number of Participants Who Received Escape Therapy
Participants who did not achieve a 20% improvement from baseline in both SJC and TJC at week 16 could, if requested and deemed necessary by the investigator, receive escape therapy, comprising adjustment of the background DMARD dose and/or treatment with a different traditional DMARD.
Measured: 24 Weeks
Change in Tender and Swollen Joint Counts From Baseline to Week 24
68 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68.
66 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.
Measured: Baseline and Week 24
Change in Participant's Global Assessment of Disease Activity From Baseline to Week 24
The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the participant. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Measured: Baseline and Week 24
Change in Physician's Global Assessment of Disease Activity From Baseline to Week 24
The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity).
Measured: Baseline and Week 24
Change in Participant's Global Assessment of Pain From Baseline to Week 24
The participants assessed their pain on a 0 to 100 mm VAS. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change indicated improvement.
Measured: Baseline and Week 24
Change in C-Reactive Protein From Baseline to Week 24
The serum concentration of CRP an acute phase inflammatory marker, is measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.
Measured: Baseline and Week 24
Change in ESR From Baseline to Week 24
The ESR was measured in mm/hour. A reduction in the level is considered an improvement.
Measured: Baseline and Week 24
Percentage of Participants With Low Disease Activity and in Clinical Remission
DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, ESR and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 less than or equal to (≤3.2) = low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24
Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score
FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in health status.
Measured: Baseline and Week 24
Mean Rheumatoid Factor at Baseline and Week 24
Rheumatoid factor (RF) is a disease characteristic and more than 85% of the participants studied were positive for the factor. These data are from patients who were RF positive. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL.
Measured: Baseline and 24 Weeks
Change in Hemoglobin From Baseline to Week 24
Levels of hemoglobin were determined in grams/liter (g/L)as a measure of anemia in participants
Measured: Baseline and 24 Weeks
Change in Health Assessment Questionnaire - Disease Index (HAQ-DI) From Baseline to Week 24
HAQ-DI is a self-completed participant questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.
Measured: Baseline and 24 Weeks
Percentage of Participants With ACR20 Response by First Week of Onset
ACR 20 responses are summarized by first onset as a percentage of the total number of responders at week 24. The number of participants first achieving an ACR20 response at each time point is represented by treatment arm as a proportion of the total number of participants that had an ACR20 response at Week 24 using n as the denominator.
Measured: Weeks 2, 4, 8, 12, 16, 20, and 24
Time to First Low Disease Activity
Time to Low disease activity was calculated as the number of days from the first dose of drug administration to the date of first achievement of DAS28≤3.2.
Measured: Weeks 2, 4, 8, 12, 16, 20, and 24
Time to First Remission
Time to first Remission was calculated as the number of days from the date of first dose of study drug administration to the date of first achievement of DAS<2.6
Measured: Weeks 2, 4, 8, 12, 16, 20, and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2008 (estimated)
- Study start31 Oct 2008
- Primary completion22 Jul 2010
- Study completion22 Jul 2010
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 209 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
- NCT00773461
- Sponsor's protocol ID
- ML21753
- Status last verified
- Jun 2017
- First submitted
- 15 Oct 2008
- Last updated
- 1 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind Study of Safety and Reduction in Signs and Symptoms During Treatment With Tocilizumab Versus Placebo, in Combination With DMARD Therapy, in Patients With Active Rheumatoid Arthritis and Inadequate Response to Current DMARD Therapy
- ClinicalTrials.gov ID
- NCT00773461
- Acronym / sponsor ID
- ML21753
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 209 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 31 Oct 2008 (actual)
- Primary completion
- 22 Jul 2010 (actual)
- Study completion
- 22 Jul 2010 (actual)
- First posted
- 16 Oct 2008 (estimated)
- Results
- Posted 21 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 2 arm study will compare the safety and efficacy, with regard to reduction of signs and symptoms, of tocilizumab versus placebo, both in combination with DMARDs, in patients with active rheumatoid arthritis who currently have an inadequate response to DMARD therapy. Patients will be randomized 2:1 to receive tocilizumab 8mg/kg iv or placebo iv every 4 weeks, in conjunction with stable DMARD therapy. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: tocilizumab [RoActemra/Actemra] |
| 2 | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- adult patients, 18-70 years of age;
- rheumatoid arthritis for >= 6 months;
- receiving permitted DMARDs, at a stable dose, for >= 8 weeks prior to baseline;
- current inadequate clinical response to DMARDs.
Key exclusion criteria (4 listed)
- major surgery, including joint surgery, within 8 weeks before entering study, or planned major surgery within 6 months following randomization;
- rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis;
- unsuccessful treatment with an anti-TNF agent;
- previous treatment with tocilizumab.
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 |
|---|---|---|
| tocilizumab [RoActemra/Actemra]8mg/kg iv every 4 weeks for 24 weeks | Drug | 1 |
| Placeboiv every 4 weeks for 24 weeks | Drug | 2 |
Primary outcome
Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24
Time frame: Week 24
To achieve an ACR20 response required at least a 20% improvement, compared with baseline, in both (tender joints count)TJC and (swollen joints count) SJC, as well as in 3 out of 5 additional ACR core set variables: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain, health assessment questionnaire disease index (HAQ-DI) and C-reactive protein (CRP). CRP was used primarily for the calculation of the ACR response; if missing, Erythrocyte Sedimentation Rate (ESR) was substituted. ITT sensitivity analysis was carried out using an alternative imputation method (last observation carried forward [LOCF]).
16 secondary outcomes
Percentage of Participants With ACR50 and ACR70 Responses at Week 24
Time frame: Week 24
Number of Participants Who Received Escape Therapy
Time frame: 24 Weeks
Change in Tender and Swollen Joint Counts From Baseline to Week 24
Time frame: Baseline and Week 24
Change in Participant's Global Assessment of Disease Activity From Baseline to Week 24
Time frame: Baseline and Week 24
Change in Physician's Global Assessment of Disease Activity From Baseline to Week 24
Time frame: Baseline and Week 24
Change in Participant's Global Assessment of Pain From Baseline to Week 24
Time frame: Baseline and Week 24
Change in C-Reactive Protein From Baseline to Week 24
Time frame: Baseline and Week 24
Change in ESR From Baseline to Week 24
Time frame: Baseline and Week 24
Percentage of Participants With Low Disease Activity and in Clinical Remission
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24
Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score
Time frame: Baseline and Week 24
Mean Rheumatoid Factor at Baseline and Week 24
Time frame: Baseline and 24 Weeks
Change in Hemoglobin From Baseline to Week 24
Time frame: Baseline and 24 Weeks
Change in Health Assessment Questionnaire - Disease Index (HAQ-DI) From Baseline to Week 24
Time frame: Baseline and 24 Weeks
Percentage of Participants With ACR20 Response by First Week of Onset
Time frame: Weeks 2, 4, 8, 12, 16, 20, and 24
Time to First Low Disease Activity
Time frame: Weeks 2, 4, 8, 12, 16, 20, and 24
Time to First Remission
Time frame: Weeks 2, 4, 8, 12, 16, 20, and 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing tocilizumab [RoActemra/Actemra] in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 9 sites in China.
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 4 inclusion and 4 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 1 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in China. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 21 Jul 2016). 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?
Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24 (time frame: Week 24). 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 1 Aug 2017.