A Study Comparing Infusion Rates of Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis

Phase II Multi-centre, Randomized, Parallel Group, Pilot Trial to Compare the Incidence of Tocilizumab Related Infusion Reactions in Moderate to Severe RA Patients When Infusion is Made Over 1 Hour Against 31 Minutes

This 2 arm study will compare the incidence of tocilizumab-related infusion reactions, using 2 different infusion times, in patients with moderate to severe rheumatoid arthritis who have shown an inadequate response to DMARDs (Disease Modifying Anti Rheumatic Drugs) or anti-TNFs.Patients will be randomized to one of 2 groups, to receive tocilizumab 8mg/kg iv every 4 weeks either a)over a 1h infusion time for all administrations or b) a 1h infusion time for the first administration, followed by a 31 minute infusion time for subsequent administrations (unless drug-related infusion reactions occur).The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: tocilizumab [RoActemra/Actemra]; Drug: tocilizumab [RoActemra/Actemra]

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Avila, Spain, 05071
  • Castellon, Spain, 12004
  • Madrid, Spain, 28031
  • Madrid, Spain, 28935
  • Zaragoza, Spain, 50009
  • Alava
    • Vitoria, Alava, Spain, 01009
  • Alicante
    • Villajoyosa, Alicante, Spain, 03570
  • Asturias
    • Gijon, Asturias, Spain, 33394
    • Oviedo, Asturias, Spain, 33006
  • Barcelona
    • Badalona, Barcelona, Spain, 08915
    • Hospitalet de Llobregat, Barcelona, Spain, 08906
    • Mollet del Valles, Barcelona, Spain, 08100
  • Cantabria
    • Torrelavega, Cantabria, Spain, 39300
  • Islas Baleares
    • Menorca, Islas Baleares, Spain, 07701
    • Palma de Mallorca, Islas Baleares, Spain, 07198
    • Palma de Mallorca, Islas Baleares, Spain, 07014
  • Madrid
    • Alcala de Henares, Madrid, Spain, 28805
    • San Sebastian de los Reyes, Madrid, Spain, 28702
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36204
    • Vigo, Pontevedra, Spain, 36214
  • Valencia
    • Alzira, Valencia, Spain, 46600
    • San Juan, Valencia, Spain, 03550
    • Valenica, Valencia, Spain, 46009
  • Vizcaya
    • Galdakao, Vizcaya, Spain, 48960

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients, >=18 years of age;
• active moderate or severe rheumatoid arthritis;
• active disease for >6 months;
• inadequate response to a stable dose of non-biologic DMARDs or antiTNFs.

Exclusion Criteria:

• rheumatic autoimmune disease other than rheumatoid arthritis;
• prior history of, or current inflammatory joint disease other than rheumatoid arthritis;
• major surgery (including joint surgery) within 8 weeks prior to screening, or planned major surgery within 6 months following enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: tocilizumab [RoActemra/Actemra]; 8mg/kg iv every 4 weeks for 6 infusions; first infusion 1h duration, subsequent infusions 31 minutes duration; Drug: tocilizumab [RoActemra/Actemra]; 8mg/kg iv every 4 weeks for 6 infusions; each infusion 1h duration
Active Comparator: 2	Drug: tocilizumab [RoActemra/Actemra]; 8mg/kg iv every 4 weeks for 6 infusions; first infusion 1h duration, subsequent infusions 31 minutes duration; Drug: tocilizumab [RoActemra/Actemra]; 8mg/kg iv every 4 weeks for 6 infusions; each infusion 1h duration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an Infusion Reaction Within 24 Hours After Infusion	An infusion reaction was defined as any adverse event (AE) that occurred during the infusion or during the 24 hours following the infusion.	Screening, Baseline, and Weeks 4, 8, 12, 16, 20, and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Discontinuing Tocilizumab in Response to an AE or Serious AE (SAE)		Weeks 4, 8, 12, 16, 20 and Final Visit
Percentage of Participants Discontinuing Tocilizumab for Any Reason		Weeks 4, 8, 12, 16, 20 and Final Visit
Percentage of Participants With a Reduction of at Least 1.2 Units on the Disease Activity Scale Based on 28-Joint Count (DAS28) by Visit	DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and Patient's Global Assessment of Disease (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 less than or equal to (≤)3.2 equals (=) low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity; DAS28 less than (<) 2.6 = remission. A reduction of at least 1.2 units was considered a clinically significant difference.	Weeks 4, 8, 12, 16, 20 and Final Visit
Percentage of Participants Achieving a DAS28 Score <3.2 by Visit	DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr), and Patient's Global Assessment of Disease (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 ≤3.2=low disease activity, DAS28 >3.2 to 5.1=moderate to high disease activity; DAS28 <2.6=remission.	Weeks 4, 8, 12, 16, 20 and Final Visit
Percentage of Participants Achieving a DAS28 Score <2.6 (Remission)	DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr) and Patient's Global Assessment of Disease (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 ≤3.2=low disease activity, DAS28 >3.2 to 5.1=moderate to high disease activity; DAS28 <2.6=remission.	Weeks 4, 8, 12, 16, 20 and Final Visit
DAS28 Score by Visit	DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr) and Patient's Global Assessment of Disease (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 ≤3.2=low disease activity, DAS28 >3.2 to 5.1=moderate to high disease activity; DAS28 <2.6=remission. Last observation carried forward (LOCF) visit took the last non-missing post-baseline available value.	Weeks 4, 8, 12, 16, 20, and Final Visit
Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response)	ACR20 response 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 (ESR or C-Reactive Protein [CRP])	Weeks 4, 8, 12, 16, 20 and Final Visit
Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response)	ACR50 response 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).	Weeks 4, 8, 12, 16, 20 and Final Visit
Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response)	ACR70 response 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).	Weeks 4, 8, 12, 16, 20 and Final Visit
Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response)	ACR90 response 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).	Weeks 4, 8, 12, 16, 20 and Final Visit
C-Reactive Protein (CRP) Levels	CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as Rheumatoid Arthritis. CRP is measured in milligrams per liter (mg/L).	Screening, Baseline, Weeks 4, 8, 12, 16, 20, and Final Visit
Erythrocyte Sedimentation Rate	ESR is an acute phase reactant measured in mm/hr. Reduction in ESR indicates improvement.	Baseline, Weeks 2, 4, 8, 12,16, 20, and 24
HAQ-DI Score by Visit	HAQ-DI is a self-reported, valid assessment of functional disability in rheumatoid arthritis. 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. HAQ-DI scores range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation.	Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24
Percentage of Participants With Improvement of at Least 0.22 in HAQ-DI	HAQ-DI is a self-reported, valid assessment of functional disability in rheumatoid arthritis. 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. HAQ-DI scores range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. An improvement of 0.22 units in HAQ-DI was considered to be a clinically significant improvement.	Weeks 4, 8, 12, 16, 20 and Final Visit

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: April 22, 2009
• First Submitted That Met QC Criteria: April 22, 2009
• First Posted (Estimate): April 23, 2009

Study Record Updates

• Last Update Posted (Estimate): October 22, 2014
• Last Update Submitted That Met QC Criteria: October 20, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: ML22254; 2008-006443-39