A Long-term Safety Extension Study of Tocilizumab in Brazilian Participants With Rheumatoid Arthritis (RA) Who Completed the Studies ML21530 and MA21488 (RITACT)

May 19, 2017 updated by: Hoffmann-La Roche

A Multicenter, Open-Label, Single-Arm Extension Study to Describe the Safety of Tocilizumab Treatment In Brazilian Patients With DMARDs Refractory Rheumatoid Arthritis Which Completed Studies ML21530 and MA21488 and Presenting an Indication of Maintaining the Tocilizumab Treatment

This multicenter, open-label, single-arm extension study will evaluate the long-term safety of tocilizumab (RoActemra/Actemra) in participants with RA. Participants who have completed the MA21488 (NCT00810199) core study and the ML21530 (NCT00754572) study and who could benefit from the study drug, according to the opinion of the investigator, will receive 8 milligrams per kilogram (mg/kg) of intravenous (IV) tocilizumab every 4 weeks. The anticipated time on study treatment is 104 weeks.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • BA
      • Salvador, BA, Brazil, 40050-410
        • Santa Casa de Misericordia de Salvador; Reumatologia
    • ES
      • Vitoria, ES, Brazil, 29043-910
        • Hospital Universitario Cassiano Antonio Moraes - UFES; Reumatologia
    • MG
      • Juiz de Fora, MG, Brazil, 36036-330
        • Centro Mineiro de Pesquisa - CMiP
    • SP
      • Campinas, SP, Brazil, 13083-888
        • Hospital das Clinicas - UNICAMP
      • Sao Jose do Rio Preto, SP, Brazil, 15090-000
        • Hospital de Base de Sao Jose do Rio Preto
      • Sao Paulo, SP, Brazil, 04026-000
        • Universidade Federal de Sao Paulo - UNIFESP; Reumatologia
      • Sao Paulo, SP, Brazil, 04266-010
        • Centro Paulista de Investigacao Clinica - CEPIC
      • Sao Paulo, SP, Brazil, 04027-000
        • Hospital Abreu Sodre - AACD;Reumatologia
      • Sao Paulo, SP, Brazil, 04039-004
        • Hospital Estadual do Servidor Publico; Reumatologia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participants who have completed their last visit in the core studies ML21530 and MA21488 and that might benefit from treatment using the study drug according to the investigator's evaluation
  • Absence of an AE or current or recent laboratory finding that would prevent the use of the 8 mg/kg dose of the tocilizumab
  • Receiving outpatient treatment
  • For women who are not postmenopausal and are not surgically sterile: agreement to use at least one adequate method of contraception

Exclusion Criteria:

  • Participants who have prematurely discontinued the core studies ML21530 and MA21488 for any reason
  • MA21488 study participants who remained untreated with tocilizumab after it's discontinuation according to the treatment-free remission criteria of MA21488 study
  • Immunization with a live/attenuated vaccine since the last administration of the study drug in the core studies ML21530 and ML21488
  • Diagnosis after the last visit of the study ML21530 or after the last visit of the study MA21488 of a rheumatic autoimmune disease other than RA, including systemic erythematous lupus (SEL), mixed connective tissue disease (MCTD), scleroderma and polymyositis, or a significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Secondary Sjogren's Syndrome and/or nodulosis with RA are allowed
  • Diagnosis after the last visit of the core study ML21530 or of the study MA21488 of an inflammatory joint disease other than RA
  • Abnormal laboratory parameters at the baseline
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
  • Evidences of a concomitant, serious and uncontrolled illness
  • Known active condition or a history of recurrent infections by bacteria, viruses, fungi, mycobacteria or other agents
  • Evidence of an active malignant disease, malignancies diagnosed in the last 10 years or breast cancer diagnosed in the last 20 years
  • Uncontrolled disease status, such as asthma or inflammatory bowel disease in which acute crises are usually treated with oral or parenteral corticosteroids
  • Current hepatic disease, as determined by the investigator
  • Active tuberculosis (TB) requiring treatment in the previous three years. Participants should be screened for latent TB according to local practice guidelines and should not be admitted into the study if latent TB is detected. Participants must not present any evidence of active TB infection at the enrollment. Participants treated for tuberculosis without recurrence in three years are allowed
  • History of alcohol, drugs or chemical abuse since the inclusion in the core studies ML21530 and MA21488

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Tocilizumab
Participants will receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant will be of 800 mg of tocilizumab. Participants may also receive disease-modifying anti-rheumatic drugs (DMARDs) in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.
Drug: DMARDs
DMARDs may be added to the tocilizumab treatment in any visit, at the discretion of the investigator, according to the local prescription information and participant's tolerance. Study protocol does not specify any particular DMARD.
Drug: Tocilizumab
Tocilizumab will be administered at 8 mg/kg IV dose every 4 weeks for 104 weeks
Other Names:
  • RoActemra; Actemra

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (NSAEs)
Time Frame: From Baseline up to approximately 2 years
An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; significant medical event, according to the investigator discretion (e.g., may represent a risk to the participant or may require medical/surgical intervention to prevent one of the outcomes mentioned above).
From Baseline up to approximately 2 years
Number of Participants With AEs Leading to Dose Modification or Study Discontinuation
Time Frame: From Baseline up to approximately 2 years
From Baseline up to approximately 2 years
Number of Participants With AEs of Special Interest
Time Frame: From Baseline up to approximately 2 years
Adverse events of special interest included following events: Infections (including opportunistic infections); myocardial infarction / acute coronary syndrome; gastrointestinal (GI) perforations and related events; malignancies; anaphylaxis/hypersensitivity reactions; demyelinating disorders; stroke; hemorrhagic events; and hepatic events. Overall number of participants who experienced any of these AEs of special interest was reported.
From Baseline up to approximately 2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and follow-up (FU) Visit 1 (Week 108), FU Visit 2 (Week 116)
DAS28 score is a measure of participant's disease activity calculated using tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), participant's global assessment of disease activity (general health [GH]) using visual analog scale (VAS), 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28 = [0.56 multiplied by (*) square root (√) of TJC28] plus (+) [0.28*√SJC28]+[0.70*the natural logarithm (ln) ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity.
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and follow-up (FU) Visit 1 (Week 108), FU Visit 2 (Week 116)
Tender Joint Count (TJC)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
An assessment of 28 joints was conducted for tenderness. Joints were assessed and classified as tender/not tender by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for tenderness.
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Swollen Joint Count (SJC)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
An assessment of 28 joints was conducted for swelling. Joints were assessed and classified as swollen/not swollen by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for swelling.
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Global Evaluation of Disease Activity by the Participant Using VAS Score
Time Frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Participant's global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as "inactive disease" (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as "disease maximum activity" (maximum activity of arthritis). The participant marked the line according to their assessment and the distance from the left edge was measured.
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Global Evaluation of Disease Activity by the Physician Using VAS Score
Time Frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Physician global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as "inactive disease" (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as "disease maximum activity" (maximum activity of arthritis). The physician marked the line according to their assessment and the distance from the left edge was measured.
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Participant's Pain Assessment Using VAS Score
Time Frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Participant's pain assessment was made on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as "no pain" and 100 mm (right end of the line) as "unbearable pain". The participant marked the line according to their assessment and the distance from the left edge was measured.
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Time Frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
The Stanford HAQ-DI is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/personal care, ability to stand-up, eating, walking, hygiene, reaching, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents 'no disability' and 3 represents 'very severe, high-dependency disability'.
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Health Assessment Questionnaire (HAQ) Pain VAS Score
Time Frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
The HAQ pain VAS is a measure of pain on a continuous 100 mm scale. Participants were asked to indicate how much pain they had in the past week as a result of their illness on a horizontal line from 0 (no pain) to 100 mm (severe pain).
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
C-Reactive Protein (CRP) Level
Time Frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
CRP is an acute phase reactant and is a measure of inflammation.
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
ESR Level
Time Frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
ESR is an acute phase reactant and is a measure of inflammation.
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 15, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 6, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 6, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 25, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 29, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 12, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ML28091

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings