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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00887341
First received: April 22, 2009
Last updated: October 20, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab [RoActemra/Actemra]
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: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With an Infusion Reaction Within 24 Hours After Infusion [ Time Frame: Screening, Baseline, and Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: Yes ]
    An infusion reaction was defined as any adverse event (AE) that occurred during the infusion or during the 24 hours following the infusion.


Secondary Outcome Measures:
  • Percentage of Participants Discontinuing Tocilizumab in Response to an AE or Serious AE (SAE) [ Time Frame: Weeks 4, 8, 12, 16, 20 and Final Visit ] [ Designated as safety issue: No ]
  • Percentage of Participants Discontinuing Tocilizumab for Any Reason [ Time Frame: Weeks 4, 8, 12, 16, 20 and Final Visit ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Weeks 4, 8, 12, 16, 20 and Final Visit ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving a DAS28 Score <3.2 by Visit [ Time Frame: Weeks 4, 8, 12, 16, 20 and Final Visit ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving a DAS28 Score <2.6 (Remission) [ Time Frame: Weeks 4, 8, 12, 16, 20 and Final Visit ] [ Designated as safety issue: No ]
    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.

  • DAS28 Score by Visit [ Time Frame: Weeks 4, 8, 12, 16, 20, and Final Visit ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) [ Time Frame: Weeks 4, 8, 12, 16, 20 and Final Visit ] [ Designated as safety issue: No ]
    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])

  • Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) [ Time Frame: Weeks 4, 8, 12, 16, 20 and Final Visit ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) [ Time Frame: Weeks 4, 8, 12, 16, 20 and Final Visit ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) [ Time Frame: Weeks 4, 8, 12, 16, 20 and Final Visit ] [ Designated as safety issue: No ]
    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).

  • C-Reactive Protein (CRP) Levels [ Time Frame: Screening, Baseline, Weeks 4, 8, 12, 16, 20, and Final Visit ] [ Designated as safety issue: No ]
    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).

  • Erythrocyte Sedimentation Rate [ Time Frame: Baseline, Weeks 2, 4, 8, 12,16, 20, and 24 ] [ Designated as safety issue: No ]
    ESR is an acute phase reactant measured in mm/hr. Reduction in ESR indicates improvement.

  • HAQ-DI Score by Visit [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Improvement of at Least 0.22 in HAQ-DI [ Time Frame: Weeks 4, 8, 12, 16, 20 and Final Visit ] [ Designated as safety issue: No ]
    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.


Enrollment: 76
Study Start Date: May 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: tocilizumab [RoActemra/Actemra]
8mg/kg iv every 4 weeks for 6 infusions; first infusion 1h duration, subsequent infusions 31 minutes duration
Active Comparator: 2 Drug: tocilizumab [RoActemra/Actemra]
8mg/kg iv every 4 weeks for 6 infusions; each infusion 1h duration

  Eligibility

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

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.
  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: NCT00887341

Locations
Spain
Vitoria, Alava, Spain, 01009
Villajoyosa, Alicante, Spain, 03570
Gijon, Asturias, Spain, 33394
Oviedo, Asturias, Spain, 33006
Badalona, Barcelona, Spain, 08915
Hospitalet de Llobregat, Barcelona, Spain, 08906
Mollet del Valles, Barcelona, Spain, 08100
Torrelavega, Cantabria, Spain, 39300
Menorca, Islas Baleares, Spain, 07701
Palma de Mallorca, Islas Baleares, Spain, 07198
Palma de Mallorca, Islas Baleares, Spain, 07014
Alcala de Henares, Madrid, Spain, 28805
San Sebastian de los Reyes, Madrid, Spain, 28702
Vigo, Pontevedra, Spain, 36204
Vigo, Pontevedra, Spain, 36214
Alzira, Valencia, Spain, 46600
San Juan, Valencia, Spain, 03550
Valenica, Valencia, Spain, 46009
Galdakao, Vizcaya, Spain, 48960
Avila, Spain, 05071
Castellon, Spain, 12004
Madrid, Spain, 28935
Madrid, Spain, 28031
Zaragoza, Spain, 50009
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: NCT00887341     History of Changes
Other Study ID Numbers: ML22254, 2008-006443-39
Study First Received: April 22, 2009
Results First Received: June 26, 2014
Last Updated: October 20, 2014
Health Authority: Spain: Ministry of Health

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 October 21, 2014