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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00887341
• Other study ID #: ML22254
• Secondary ID: 2008-006443-39
• Status: Completed
• Phase: Phase 2
• First received: April 22, 2009
• Last updated: October 20, 2014
• Start date: May 2009
• Est. completion date: December 2010

Study information

• Verified date: October 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• tocilizumab [RoActemra/Actemra]
8mg/kg iv every 4 weeks for 6 infusions; first infusion 1h duration, subsequent infusions 31 minutes duration
• tocilizumab [RoActemra/Actemra]
8mg/kg iv every 4 weeks for 6 infusions; each infusion 1h duration

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Percentage of Participants Discontinuing Tocilizumab in Response to an AE or Serious AE (SAE)		Weeks 4, 8, 12, 16, 20 and Final Visit	No
Secondary	Percentage of Participants Discontinuing Tocilizumab for Any Reason		Weeks 4, 8, 12, 16, 20 and Final Visit	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No