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

Phase 2

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: Tocilizumab

• Registration Number: NCT01468077
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-11
• Study First Submitted: 2011-11-07
• Study First Submitted QC: 2011-11-07
• Study First Posted: 2011-11-09
• Primary Completion: 2013-09
• Study Completion: 2013-09
• Results First Submitted: 2015-06-23
• Status Verified: 2015-07
• Results First Submitted QC: 2015-07-20
• Last Update Submitted: 2015-07-20
• Results First Posted: 2015-08-17
• Last Update Posted: 2015-08-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tocilizumab, Normal Administration	Tocilizumab	Tocilizumab 8 mg/kg infusion of 60 minutes duration every 4 weeks for 6 infusions (up to 24 weeks)
Tocilizumab, Fast Administration	Tocilizumab	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

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Any Infusion Reaction	Baseline (Day 1), and Weeks 4, 8, 12, 16, and 20	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

Name	Time	Method
Percentage of Participants Discontinuing Tocilizumab in Response to an AE or a Serious Adverse Event (SAE)	Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, and 24	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 Achieving ACR 70% Improvement (ACR70 Response) by Visit, Among Participants Who Completed All Visits	Weeks 4, 8, 12, 16, 20 and 24	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 With Improvement of at Least 0.22 Units in M-HAQ Compared to Baseline Per Visit Among Participants Who Completed All Visits	Weeks 4, 8. 12, 20, and 24	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 Achieving a DAS28 Score Below 2.6 (Remission) by Visit Among Participants Who Completed All Visits	Weeks 4, 8, 12, 16, 20, and 24	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 ACR 50% Improvement (ACR50 Response) by Visit Among Participants Who Completed All Visits	Weeks, 4, 8, 12, 16, 20, and 24	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).
High Sensitivity C-Reactive Protein (hsCRP) Levels by Visit Among Participants Who Completed All Visits	Screening, Baseline, Weeks 4, 8, 12, 16, 20, and 24	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.
Percentage of Participants Discontinuing Tocilizumab for Other Reasons	Baseline and Weeks, 4, 8, 12, 16, 20, and 24	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	Baseline and Weeks 4, 8, 12, 16, 20, and 24	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 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	Weeks 4, 8, 12, 16, 20, and 24	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 With Increased Lipid Values by Visit Among Participants Who Completed All Visits	Screening and Weeks 4, 8, 12, 16, 20, and 24	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 Achieving a DAS28 Score Below 3.2 (Low Disease Activity) by Visit Among Participants Who Completed All Visits	Weeks 4, 8, 12, 16, 20, and 24	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	Baseline, Weeks, 4, 8, 12, 16, 20, and 24	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	Weeks 4, 8, 12, 16, 20, and 24	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 90% Improvement (ACR90 Response) by Visit Among Participants Who Completed All Visits	Weeks 4, 8, 12, 16, 20 and 24	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).
Modified Health Assessment Questionnaire (M-HAQ) Score by Visit Among Participants Who Completed All Visits	Baseline, Weeks 4, 8, 12, 20, and 24	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.