A Study in Patients With Moderate to Severe Active Rheumatoid Arthritis Comparing Different Infusion Durations of RoActemra/Actemra (Tocilizumab) Treatment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01468077
First received: November 7, 2011
Last updated: July 20, 2015
Last verified: July 2015
  Purpose

This multi-center, randomized, parallel-group, active-controlled, open-label study will evaluate the safety and efficacy of a shortened RoActemra/Actemra (tocilizumab) infusion time compared to the normal infusion time. Patients will be randomized to 8 mg/kg RoActemra/Actemra infusion of 31 minutes every 4 weeks or to RoActemra/Actemra 8 mg/kg infusion of 60 minutes every 4 weeks. The anticipated time on study treatment is 24 weeks.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Tocilizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter, Randomized, Parallel Group Study to Compare the Incidence of Tocilizumab Related Infusion Reactions in Patients With Moderate to Severe Active RA, When Infusion is Given Over 31 Minutes Compared to 1 Hour

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Any Infusion Reaction [ Time Frame: Baseline (Day 1), and Weeks 4, 8, 12, 16, and 20 ] [ Designated as safety issue: No ]
    An infusion reaction was defined as any adverse event (AE) that occurred during the infusion or during the 24 hours following the infusion and deemed possibly or probably related to tocilizumab.


Secondary Outcome Measures:
  • Percentage of Participants Discontinuing Tocilizumab in Response to an AE or a Serious Adverse Event (SAE) [ Time Frame: Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    All occurrences of participants who received at least 1 infusion of tocilizumab and then stopped tocilizumab infusions due to an AE or SAE were analyzed.

  • Percentage of Participants Discontinuing Tocilizumab for Other Reasons [ Time Frame: Baseline and Weeks, 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    Participants that stopped the administration of tocilizumab and discontinued the study prematurely due to reasons other than an AE or SAE were analyzed.

  • Percentage of Participants With Increased Liver Enzyme Values of Greater Than (>)1.5 Times, or >3 Times, or >5 Times Over the Upper Limit of Normal (ULN) by Visit Among Participants Who Completed All Visits [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]

    Increased liver enzyme values defined as Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) values of >1.5 times, or >3 times, or >5 times over the ULN. Almost none of the participants had increased measurements of AST, thus only values of ALT were presented. None of the participants presented with increased values of ALT above 3 or 5 ULN at any of the visits.

    ITT Completers is defined as a subset of the participants in the ITT population who completed all study visits.


  • Percentage of Participants With Increased Lipid Values by Visit Among Participants Who Completed All Visits [ Time Frame: Screening and Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    Increased levels of high density lipoproteins (HDL) equal to or greater than (≥)1.5 millimoles per liter (mmol/L), and low density lipoproteins (LDL) ≥4.1 mmol/L, and total cholesterol ≥5.1 mmol/L, are defined according to the Adult Treatment Panel III (ATP-III) guidelines.

  • Percentage of Participants With a Reduction of at Least 1.2 Points in Disease Activity Score Based on 28-Joint Count (DAS28) by Visit Among Participants Who Completed All Visits [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    Improvement in Rheumatoid Arthritis (RA) disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response High sensitivity C-Reactive Protein (hsCRP), and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in the DAS28 score during the study period. A low disease activity was defined as a DAS28 score less than (<)3.2, and remission was defined as a DAS28 score <2.6.

  • Percentage of Participants Achieving a DAS28 Score Below 3.2 (Low Disease Activity) by Visit Among Participants Who Completed All Visits [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response hsCRP, and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in the DAS28 score during the study period. A low disease activity was defined as a DAS28 score <3.2, and remission was defined as a DAS28 score <2.6.

  • Percentage of Participants Achieving a DAS28 Score Below 2.6 (Remission) by Visit Among Participants Who Completed All Visits [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response hsCRP, and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in the DAS28 score during the study period. A low disease activity was defined as a DAS28 score <3.2, and remission was defined as a DAS28 score <2.6.

  • DAS28 Score by Visit Among Participants Who Completed All Visits [ Time Frame: Baseline, Weeks, 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response hsCRP, and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in the DAS28 score during the study period. A low disease activity was defined as a DAS28 score <3.2, and remission was defined as a DAS28 score <2.6.

  • Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) by Visit Among Participants Who Completed All Visits [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    ACR20 response is defined as an improvement of ≥20% in swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) as well as ≥20% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; Health Assessment Questionnaire - Disability Index (HAQ-DI); and acute phase reactive factors (Erythrocyte Sedimentation Rate [ESR] or C-Reactive Protein [CRP]).

  • Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) by Visit Among Participants Who Completed All Visits [ Time Frame: Weeks, 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    ACR50 response is defined as an improvement of ≥50% in SJC (66 joints) and TJC (68 joints) as well as ≥50% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).

  • Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) by Visit, Among Participants Who Completed All Visits [ Time Frame: Weeks 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    ACR70 response is defined as an improvement of ≥70% in SJC (66 joints) and TJC (68 joints) as well as ≥70% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).

  • Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) by Visit Among Participants Who Completed All Visits [ Time Frame: Weeks 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    ACR90 response is defined as an improvement of ≥90% in SJC (66 joints) and TJC (68 joints) as well as ≥90% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).

  • High Sensitivity C-Reactive Protein (hsCRP) Levels by Visit Among Participants Who Completed All Visits [ Time Frame: Screening, Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    hsCRP is a marker for inflammation and is measured in milligrams per liter (mg/L). High levels of this protein indicate inflammation in diseases such as RA.

  • Modified Health Assessment Questionnaire (M-HAQ) Score by Visit Among Participants Who Completed All Visits [ Time Frame: Baseline, Weeks 4, 8, 12, 20, and 24 ] [ Designated as safety issue: No ]
    M-HAQ is a self-reported, valid assessment of functional disability in RA. Assessment based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. Scores range 0 to 3; without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3.

  • Percentage of Participants With Improvement of at Least 0.22 Units in M-HAQ Compared to Baseline Per Visit Among Participants Who Completed All Visits [ Time Frame: Weeks 4, 8. 12, 20, and 24 ] [ Designated as safety issue: No ]
    M-HAQ is a self-reported, valid assessment of functional disability in RA. Assessment based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. Scores range 0 to 3; without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3.


Enrollment: 47
Study Start Date: November 2011
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab, Normal Administration
Tocilizumab 8 mg/kg infusion of 60 minutes duration every 4 weeks for 6 infusions (up to 24 weeks)
Drug: Tocilizumab
8 mg/kg infusion
Other Names:
  • RoActemra
  • Actemra
Experimental: Tocilizumab, Fast Administration
Tocilizumab 8 mg/kg infusion of 31 minutes duration every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour. If an infusion reaction occurred during any treatment, 1 hour infusions were used for all subsequent infusions
Drug: Tocilizumab
8 mg/kg infusion
Other Names:
  • RoActemra
  • Actemra

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, at least 18 years of age, inclusive
  • Diagnosis of rheumatoid arthritis of at least 6 months duration
  • Moderate to severe active rheumatoid arthritis (DAS28 >/=3.2)
  • Patients received at least 1 disease-modifying anti-rheumatic drug (DMARD) and/or 1 or more TNFalfa-inhibitors over a period of at least 8 weeks

Exclusion Criteria:

  • Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 6 months following randomization
  • Rheumatic autoimmune disease other than rheumatoid arthritis
  • Prior history of or current inflammatory joint disease other than rheumatoid arthritis
  • Functional class IV (ACR criteria)
  • History of severe allergic reaction to human, humanized or murine monoclonal antibodies
  • Known active current or history of recurrent infection (including tuberculosis)
  • Primary or secondary immunodeficiency (history of or currently active)
  • Body weight >150 kg
  • Previous treatment with any cell-depleting therapies
  • Previous treatment with tocilizumab
  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: NCT01468077

Locations
Denmark
Alborg, Denmark, 9000
Frederiksberg, Denmark, 2000
Hellerup, Denmark, 2900
Holbæk, Denmark, 4300
Odense, Denmark, 5000
Silkeborg, Denmark, 8600
Svendborg, Denmark, 5700
Iceland
Reykjavik, Iceland, 108
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01468077     History of Changes
Other Study ID Numbers: ML27901
Study First Received: November 7, 2011
Results First Received: June 23, 2015
Last Updated: July 20, 2015
Health Authority: Denmark: Danish Medicines Agency

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

ClinicalTrials.gov processed this record on September 03, 2015