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A Long-Term Extension Study of WA19926 on the Safety of Tocilizumab (RoActemra/Actemra) in Participants With Early Moderate to Severe Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01655381
First received: July 30, 2012
Last updated: December 7, 2016
Last verified: December 2016
  Purpose
This open-label, single arm, multicenter long-term extension study will evaluate the safety and efficacy of tocilizumab (RoActemra/Actemra) in participants with moderate to severe rheumatoid arthritis who have completed the 104-week WA19926 core study. Eligible participants will receive tocilizumab 8 mg/kg intravenously every 4 weeks for up to 104 weeks.

Condition Intervention Phase
Rheumatoid Arthritis Drug: Tocilizumab Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Single Arm, Long-term Extension Study of WA19926 to Describe Safety During Treatment With Tocilizumab in Patients With Early, Moderate to Severe Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Any Adverse Event (AE) [ Time Frame: Up to 160 weeks ]
    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any AE that is fatal; life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect in a neonate/infant or significant medical event in the Investigator's judgment. AE of special interest (AESI) includes serious and/or medically significant infectious; myocardial infarction(MI) / acute coronary syndrome (ACS); gastrointestinal (GI) perforation; anaphylaxis / hypersensitivity reactions; demyelinating disorders; stroke; serious and/or medically significant bleeding events; serious and/or medically significant hepatic events; malignancies malignant.


Secondary Outcome Measures:
  • Percentage of Participants With at Least One Clinical Remission Period [ Time Frame: Up to approximately 148 weeks ]
    Clinical remission: Disease Activity Score Based on 28-joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) less than (<)2.6 and/or Simplified Disease Activity Index (SDAI) less than or equal to (≤)3.3 for a period of at least two consecutive assessment visits (every 12 weeks) over the extension study period. DAS28-ESR was calculated using Swollen Joint Count Based on 28 Joints (SJC28), Tender Joint Count Based on 28 Joints (TJC28), ESR (mm/hour) and patient's global assessment of disease activity (100-millimeter (mm) horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity. DAS28-ESR scores range from 0-10, with higher scores corresponding to greater disease activity. SDAI was calculated using SJC28, TJC28, C-reactive protein (CRP) (milligrams per liter (mg/L)), the patient's global assessment of disease activity and physician's global assessment of disease activity; SDAI scores range from 0-86, where lower scores indicate less disease activity.

  • Percentage of Participants With at Least One Drug-Free Period [ Time Frame: Up to approximately 148 weeks ]
    Drug-free remission period was defined as clinical remission for at least 2 consecutive assessment visits (every 12 weeks) AND without tocilizumab administration during this clinical remission period.

  • Cumulative Time of Remission Per Participant Over the Extension Study Period [ Time Frame: Up to approximately 148 weeks ]
    Clinical remission was defined as DAS28-ESR <2.6 and/or SDAI ≤3.3 for a period of at least two consecutive assessment visits (every 12 weeks) over the extension study period. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity. SDAI scores range from 0 to 86, where lower scores indicate less disease activity.

  • Percentage of Participants With at Least 1 Rheumatoid Arthritis (RA) Flare [ Time Frame: Up to approximately 148 weeks ]
    An RA flare was defined as an increase in DAS28-ESR from the previous available visits of >1.2, or >0.6 if current DAS28-ESR ≥3.2. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.

  • Time to RA Flare Following Remission or Drug-Free Remission [ Time Frame: Up to approximately 148 weeks ]
    Time to RA flare was defined as period of clinical remission or drug-free remission followed by flare of DAS28-ESR (increase in DAS28-ESR from the previous available visits of >1.2, or >0.6 if current DAS28-ESR ≥3.2). In the case of several remission periods for the same participant, the largest period was used.

  • Change From Day 1 in DAS28-ESR Scores Over Time [ Time Frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140 ]
    DAS28-ESR was calculated using Swollen Joint Count Based on 28 Joints (SJC28), Tender Joint Count Based on 28 Joints (TJC28), ESR (mm/hour) and patient's global assessment of disease activity (100-millimeter (mm) horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.

  • Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time [ Time Frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140 ]
    SDAI was calculated using SJC28, TJC28, C-reactive protein (CRP) (milligrams per liter (mg/L)), and the patient's global assessment of disease activity and physician's global assessment of disease activity; SDAI scores range from 0 to 86, where lower scores indicate less disease activity.

  • Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time [ Time Frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140 ]
    The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28 tender joints. Higher scores correspond to greater disease activity.

  • Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time [ Time Frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140 ]
    The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28 swollen joints. Higher scores correspond to greater disease activity.

  • Erythrocyte Sedimentation Rate (ESR) Over Time [ Time Frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140 ]
    ESR is an direct measure of how much inflammation is in the body. The normal range is 0-22 mm/hour for men and 0-29 mm/hour for women. Higher scores correspond to greater disease activity.

  • C-reactive Protein (CRP) Level [ Time Frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140 ]
    C-reactive protein (CRP) is a blood test marker for inflammation in the body. Normal CRP levels are below 5 milligrams per liter (mg/L). Higher scores correspond to greater disease activity.

  • Participants' Global Assessment of Pain (VAS) Score [ Time Frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140 ]
    The participants' global assessment of pain (VAS) was assessed using a 100-mm horizontal VAS with 0=no pain to 100=maximum pain.

  • Participants' Global Assessment of Disease Activity (VAS) Score [ Time Frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140 ]
    The participants' global assessment of disease activity (VAS) was assessed using a 100-mm horizontal VAS with 0=no disease activity to 100=maximum disease.

  • Physicians' Global Assessment of Disease Activity (VAS) Score [ Time Frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140 ]
    The physicians' global assessment of disease activity (VAS) was assessed using a 100-mm horizontal VAS with 0=no disease activity to 100=maximum disease.

  • Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission [ Time Frame: Baseline and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128 140 ]

    HAQ-DI remission was defined as HAQ-DI score <0.5.

    HAQ-DI is the 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.


  • Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI [ Time Frame: Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140 ]

    Clinically meaningful improvement was defined as an improvement in HAQ-DI score of ≥0.22.

    HAQ-DI is the 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.



Enrollment: 15
Study Start Date: April 2012
Study Completion Date: July 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab
Tocilizumab 8 milligrams per kilogram (mg/kg) administered intravenously once every 4 weeks during a minimum of 104 weeks.
Drug: Tocilizumab
Tocilizumab 8 mg/kg administered intravenously.
Other Names:
  • RoActemra®
  • Actemra®

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult participants, >/= 18 years of age
  • Participants who complete their last WA19926 core study visit (Week 104) and who may benefit from study drug treatment, at baseline or later if they are in remission DAS28 at Week 104 of WA19926, according to the Investigator's assessment
  • No current or recent adverse event or laboratory finding preventing the use of the study drug dose of tocilizumab 8 mg/kg at baseline visit
  • Women of childbearing potential must agree to use adequate contraception as defined by protocol during and up to 3 months after treatment

Exclusion Criteria:

  • Pregnant females
  • Participants who have withdrawn prematurely from the WA19926 core study for any reason
  • Treatment with any investigational agent or cell-depleting therapies since the last administration of study drug in WA19926
  • Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL) 1 agent, or a T-cell costimulation modulator since the last administration of study drug in WA19926
  • Immunization with a live/attenuated vaccine since the last administration of study drug in WA19926
  • Diagnosis since last WA19926 visit (Week 104) of rheumatic autoimmune disease other than rheumatoid arthritis
  • Diagnosis since last WA19926 visit (Week 104) of inflammatory joint disease other than rheumatoid arthritis
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, including tocilizumab and its excipients
  • Evidence of severe uncontrolled concomitant disease or disorder
  • Known active or history of recurrent infections
  • Active tuberculosis requiring treatment in the previous 3 years
  • History of alcohol, drug or chemical abuse since inclusion in the WA19926 study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01655381

Locations
France
Cahors, France, 46005
Montpellier, France, 34295
Mulhouse, France, 68070
Orleans, France, 45032
Paris, France, 75651
Toulouse, France, 31059
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01655381     History of Changes
Other Study ID Numbers: ML28174
2011-005516-29 ( EudraCT Number )
Study First Received: July 30, 2012
Results First Received: October 7, 2016
Last Updated: December 7, 2016

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on June 23, 2017