AzTrials
AzTrials

Rheumatoid ArthritisPhase 4NCT01149057

A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-Biologic and/or Biologic DMARDS

A Phase 4 study testing tocilizumab [RoActemra/Actemra] in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 16 sites in Israel.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This single arm, open-label study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with active, moderate to severe rheumatoid arthritis who have an inadequate response to non-biologic and/or biologic disease-modifying antirheumatic drugs (DMARDs). 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?
tocilizumab [RoActemra/Actemra]
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
145 participants
Where
16 sitesIsrael
Study dates
Oct 2010to Jul 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
  • Inadequate response to >/=3 DMARDs (non-biologic and/or biologic)
  • Current treatment at stable dose for >/=8 weeks
  • Etanercept discontinued >/=2 weeks, Anakinra >/=1 week, Infliximab, Adalimumab, Abatacept, Golimumab, Certolizumab >/=4 weeks, prior to baseline visit. Patients have discontinued MabThera/Rituxan or Ocrelizumab >/=16 weeks, and must have proven B-cell repletion

Who cannot join

  • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline
  • Rheumatic autoimmune disease other than RA
  • Functional class IV (American College of Rheumatology Classification)
  • Prior history or current inflammatory joint disease other than RA
  • Oral corticosteroids at a dose of >10 mg/day prednisone equivalent
  • Positive hepatitis B surface antigen (HBsAg) and / or total hepatitis B core antibodies (HBcAb) or hepatitis C virus (HCV) antibody
  • Current or history of recurrent bacterial, viral, fungal or mycobaterial infection
  • History of or currently active primary or secondary immunodeficiency

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

Israel16 sites
  • Study site

    Afula, 18101

  • Study site

    Ashkelon, 78306

  • Study site

    Beer Yaakov, 6093000

  • Study site

    Beersheba, 8410101

  • Study site

    Hadera, 38100

  • Study site

    Haifa, 3109601

  • Study site

    Haifa, 3339419

  • Study site

    Haifa, 34362

  • Study site

    Holon, 58100

  • Study site

    Jerusalem, 9112001

  • Study site

    Jerusalem, 91240

  • Study site

    Kfar Saba, 44281

  • Study site

    Petah Tikva, 4941492

  • Study site

    Ramat Gan, 5262000

  • Study site

    Rehovot, 76100

  • Study site

    Tel Aviv, 6423906

Other trials in Israel

About this study

Official title: An Open-Label Study to Evaluate the Efficacy and Safety Of Tocilizumab in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-biologic DMARDs and/or Biologic DMARDs

This single arm, open-label study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with active, moderate to severe rheumatoid arthritis who have an inadequate response to non-biologic and/or biologic disease-modifying antirheumatic drugs (DMARDs). Patients will receive intravenous RoActemra/Actemra at a dose of 8 mg/kg every 4 weeks. Anticipated time on study treatment is 96 weeks.

Being tested
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.

  • tocilizumab [RoActemra/Actemra]Drug

    8 mg/kg intravenously, every 4 weeks for 96 weeks

Study groups in NCT01149057
Study groupRoleWhat they receive
Single ArmExperimentalNot described
Receives: Drug: tocilizumab [RoActemra/Actemra]

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 24 in Intent-to-treat (ITT) Population

    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants 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 participant's 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 (worst score) to 52 (best score).

    Measured: Baseline, Week 24

  2. Change From Baseline in FACIT Fatigue Score at Week 48 in ITT Population

    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants 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 participant's 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 (worst score) to 52 (best score).

    Measured: Baseline, Week 48

  3. Change From Baseline in FACIT Fatigue Score at Week 72 in ITT Population

    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants 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 participant's 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 (worst score) to 52 (best score).

    Measured: Baseline, Week 72

  4. Change From Baseline in FACIT Fatigue Score at Week 96 in ITT Population

    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants 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 participant's 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 (worst score) to 52 (best score).

    Measured: Baseline, Week 96

  5. Change From Baseline in FACIT Fatigue Score at Week 24 in Per Protocol (PP) Population

    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants 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 participant's 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 (worst score) to 52 (best score).

    Measured: Baseline, Week 24

  6. Change From Baseline in FACIT Fatigue Score at Week 48 in PP Population

    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants 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 participant's 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 (worst score) to 52 (best score).

    Measured: Baseline, Week 48

  7. Change From Baseline in FACIT Fatigue Score at Week 72 in PP Population

    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants 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 participant's 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 (worst score) to 52 (best score).

    Measured: Baseline, Week 72

  8. Change From Baseline in FACIT Fatigue Score at Week 96 in PP Population

    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants 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 participant's 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 (worst score) to 52 (best score).

    Measured: Baseline, Week 96

Secondary outcomes (14)
  1. Change From Baseline in Bone Mineral Density (BMD) in Lumbar Spine, Total Hip and Femoral Neck Regions at End of Study

    BMD was measured by dual energy X-ray absorptiometry (DXA) and T-scores (a standard deviation [SD] compared with the peak BMD value of an adult aged from 20 to 30 years) were calculated. Osteopenia was defined by a T-score between -1 and -2.5 SD and osteoporosis as a T-score below -2.5 SD, according to the World Health Organization (WHO) guidelines. T-scores for L1-L4 lumbar spine, total spine, total hip (left), and femoral neck (left) were calculated.

    Measured: Baseline, End of the study (up to Week 100)

  2. Number of Participants Achieving Remission According to Disease Activity Score 28 (DAS28) at Weeks 24, 48, 72, and 96

    Remission was defined as DAS28 score less than (<) 2.6. The DAS28 score was a measure of the participant's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity (visual analog scale [VAS]: 0=no disease activity to 100=maximum disease activity) and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. In case of missing ESR value, C-Reactive Protein (CRP) was used to calculate DAS28. Higher scores represented higher disease activity.

    Measured: Weeks 24, 48, 72 and 96

  3. Percentage of Participants Achieving Remission According to DAS28 at Weeks 24, 48, 72, and 96

    Remission was defined as DAS28 score <2.6. The DAS28 score was a measure of the participant's disease activity calculated using the TJC [28 joints], SJC [28 joints], patient's global assessment of disease activity (VAS: 0=no disease activity to 100=maximum disease activity) and the ESR for a total possible score of 0 to approximately 10. In case of missing ESR value, CRP was used to calculate DAS28. Higher scores represented higher disease activity.

    Measured: Weeks 24, 48, 72 and 96

  4. Percentage of Participants With DAS28 Good or Moderate European League Against Rheumatism (EULAR) Response at Weeks 24, 48, 72 and 96

    The DAS28 score was a measure of the participant's disease activity calculated using the TJC [28 joints], SJC [28 joints], patient's global assessment of disease activity (VAS: 0=no disease activity to 100=maximum disease activity) and the ESR for a total possible score of 0 to approximately 10. In case of missing ESR value, CRP was used to calculate DAS28. Higher scores represented higher disease activity. EULAR Good response: DAS28 ≤3.2 and a change from Baseline <-1.2. EULAR Moderate response: DAS28 greater than (>) 3.2 to less than or equal to (≤) 5.1 or a change from Baseline <-0.6 to greater than or equal to (≥) -1.2.

    Measured: Weeks 24, 48, 72 and 96

  5. Percentage of Participants Achieving Remission and Low Disease Activity According to Simplified Disease Activity Index (SDAI) at Weeks 24, 48, 72, and 96

    SDAI was calculated by a simple numerical sum of tender and swollen joint count (based on a 28-joint assessment), patient and physician global assessment of disease activity (VAS 0-10 centimeter [cm]), and level of CRP. SDAI total score 0-86; higher scores = greater effect due to disease activity. Remission was defined as SDAI score ≤3.3. Low disease activity was defined as SDAI score ≤11.0.

    Measured: Weeks 24, 48, 72 and 96

  6. Percentage of Participants Achieving Remission and Low Disease Activity According to Clinical Disease Activity Index (CDAI) at Weeks 24, 48, 72, and 96

    CDAI was calculated by a simple numerical sum of tender and swollen joint count (based on 28-joint assessment) and the patient and physician global disease assessment (VAS 0-10 cm). CDAI total score 0-76; higher scores = greater effect due to disease activity. Remission was defined as CDAI score ≤2.8. Low disease activity was defined as CDAI score ≤10.0.

    Measured: Weeks 24, 48, 72 and 96

  7. Change From Baseline in TJC At Weeks 24, 48, 72, and 96

    68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from baseline indicated improvement.

    Measured: Baseline; Weeks 24, 48, 72 and 96

  8. Change From Baseline in SJC At Weeks 24, 48, 72, and 96

    66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from baseline indicated improvement.

    Measured: Baseline; Weeks 24, 48, 72 and 96

  9. Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96

    ACR20 response: ≥20% improvement in TJC; ≥20% improvement in SJC; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; Patient Global Assessment of Disease Activity (PtGA); Physician Global Assessment of Disease Activity (PGA); self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ-DI]); and either CRP or ESR. ACR50 response required ≥50% improvement in the above criteria and ACR70 response required ≥70% improvement in the above criteria.

    Measured: Weeks 24, 48, 72 and 96

  10. Change From Baseline in Hemoglobin at Weeks 20, 44, 72 and 96

    Measured: Baseline; Weeks 20, 44, 72 and 96

  11. C-reactive Protein Level

    Measured: Baseline; Weeks 8, 16, 24, 36 48, 72 and 96

  12. Erythrocyte Sedimentation Rate

    Measured: Baseline; Weeks 8, 16, 24, 36 48, 72 and 96

  13. Participant Assessment of Pain (VAS)

    The mean score of pain as assessed by participants using a 100-mm horizontal VAS, where the left endpoint (0) indicated "No pain," and the right endpoint (100) indicated "Unbearable pain". Higher score indicated higher pain.

    Measured: Baseline; Weeks 8, 16, 24, 36 48, 72 and 96

  14. Change From Baseline in Health Assessment Questionnaire (HAQ) at Weeks 24, 48, 72, and 96

    HAQ: 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: Baseline; Weeks 24, 48, 72 and 96

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jun 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionJul 2014
  4. Study completionJul 2014

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
145 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01149057
Sponsor's protocol ID
ML22873
Status last verified
Nov 2016
First submitted
22 Jun 2010
Last updated
2 Nov 2016

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing tocilizumab [RoActemra/Actemra] in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 16 sites in Israel.

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 8 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 2 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Israel. 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 29 Oct 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 From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 24 in Intent-to-treat (ITT) Population (time frame: Baseline, Week 24). The study lists 8 primary outcomes in all. 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 2 Nov 2016.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in