A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-Biologic and/or Biologic DMARDS

Rheumatoid Arthritis Clinical Trial

Official title:

An Open-Label Study to Evaluate the Efficacy and Safety Of Tocilizumab in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-biologic DMARDs and/or Biologic DMARDs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01149057
• Other study ID #: ML22873
• Status: Completed
• Phase: Phase 4
• First received: June 22, 2010
• Last updated: November 1, 2016
• Start date: October 2010
• Est. completion date: July 2014

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This single arm, open-label study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with active, moderate to severe rheumatoid arthritis who have an inadequate response to non-biologic and/or biologic disease-modifying antirheumatic drugs (DMARDs). Patients will receive intravenous RoActemra/Actemra at a dose of 8 mg/kg every 4 weeks. Anticipated time on study treatment is 96 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 145
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients, >/=18 years of age

• Active moderate to severe rheumatoid arthritis

• Inadequate response to >/=3 DMARDs (non-biologic and/or biologic)

• Current treatment at stable dose for >/=8 weeks

• Etanercept discontinued >/=2 weeks, Anakinra >/=1 week, Infliximab, Adalimumab, Abatacept, Golimumab, Certolizumab >/=4 weeks, prior to baseline visit. Patients have discontinued MabThera/Rituxan or Ocrelizumab >/=16 weeks, and must have proven B-cell repletion

Exclusion Criteria:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline

• Rheumatic autoimmune disease other than RA

• Functional class IV (American College of Rheumatology Classification)

• Prior history or current inflammatory joint disease other than RA

• Oral corticosteroids at a dose of >10 mg/day prednisone equivalent

• Positive hepatitis B surface antigen (HBsAg) and / or total hepatitis B core antibodies (HBcAb) or hepatitis C virus (HCV) antibody

• Current or history of recurrent bacterial, viral, fungal or mycobaterial infection

• History of or currently active primary or secondary immunodeficiency

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• tocilizumab [RoActemra/Actemra]
8 mg/kg intravenously, every 4 weeks for 96 weeks

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Clalit Health Services

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 24 in Intent-to-treat (ITT) Population	The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).	Baseline, Week 24	No
Primary	Change From Baseline in FACIT Fatigue Score at Week 48 in ITT Population	The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).	Baseline, Week 48	No
Primary	Change From Baseline in FACIT Fatigue Score at Week 72 in ITT Population	The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).	Baseline, Week 72	No
Primary	Change From Baseline in FACIT Fatigue Score at Week 96 in ITT Population	The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).	Baseline, Week 96	No
Primary	Change From Baseline in FACIT Fatigue Score at Week 24 in Per Protocol (PP) Population	The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).	Baseline, Week 24	No
Primary	Change From Baseline in FACIT Fatigue Score at Week 48 in PP Population	The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).	Baseline, Week 48	No
Primary	Change From Baseline in FACIT Fatigue Score at Week 72 in PP Population	The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).	Baseline, Week 72	No
Primary	Change From Baseline in FACIT Fatigue Score at Week 96 in PP Population	The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).	Baseline, Week 96	No
Secondary	Change From Baseline in Bone Mineral Density (BMD) in Lumbar Spine, Total Hip and Femoral Neck Regions at End of Study	BMD was measured by dual energy X-ray absorptiometry (DXA) and T-scores (a standard deviation [SD] compared with the peak BMD value of an adult aged from 20 to 30 years) were calculated. Osteopenia was defined by a T-score between -1 and -2.5 SD and osteoporosis as a T-score below -2.5 SD, according to the World Health Organization (WHO) guidelines. T-scores for L1-L4 lumbar spine, total spine, total hip (left), and femoral neck (left) were calculated.	Baseline, End of the study (up to Week 100)	No
Secondary	Number of Participants Achieving Remission According to Disease Activity Score 28 (DAS28) at Weeks 24, 48, 72, and 96	Remission was defined as DAS28 score less than (<) 2.6. The DAS28 score was a measure of the participant's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity (visual analog scale [VAS]: 0=no disease activity to 100=maximum disease activity) and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. In case of missing ESR value, C-Reactive Protein (CRP) was used to calculate DAS28. Higher scores represented higher disease activity.	Weeks 24, 48, 72 and 96	No
Secondary	Percentage of Participants Achieving Remission According to DAS28 at Weeks 24, 48, 72, and 96	Remission was defined as DAS28 score <2.6. The DAS28 score was a measure of the participant's disease activity calculated using the TJC [28 joints], SJC [28 joints], patient's global assessment of disease activity (VAS: 0=no disease activity to 100=maximum disease activity) and the ESR for a total possible score of 0 to approximately 10. In case of missing ESR value, CRP was used to calculate DAS28. Higher scores represented higher disease activity.	Weeks 24, 48, 72 and 96	No
Secondary	Percentage of Participants With DAS28 Good or Moderate European League Against Rheumatism (EULAR) Response at Weeks 24, 48, 72 and 96	The DAS28 score was a measure of the participant's disease activity calculated using the TJC [28 joints], SJC [28 joints], patient's global assessment of disease activity (VAS: 0=no disease activity to 100=maximum disease activity) and the ESR for a total possible score of 0 to approximately 10. In case of missing ESR value, CRP was used to calculate DAS28. Higher scores represented higher disease activity. EULAR Good response: DAS28 =3.2 and a change from Baseline <-1.2. EULAR Moderate response: DAS28 greater than (>) 3.2 to less than or equal to (=) 5.1 or a change from Baseline <-0.6 to greater than or equal to (=) -1.2.	Weeks 24, 48, 72 and 96	No
Secondary	Percentage of Participants Achieving Remission and Low Disease Activity According to Simplified Disease Activity Index (SDAI) at Weeks 24, 48, 72, and 96	SDAI was calculated by a simple numerical sum of tender and swollen joint count (based on a 28-joint assessment), patient and physician global assessment of disease activity (VAS 0-10 centimeter [cm]), and level of CRP. SDAI total score 0-86; higher scores = greater effect due to disease activity. Remission was defined as SDAI score =3.3. Low disease activity was defined as SDAI score =11.0.	Weeks 24, 48, 72 and 96	No
Secondary	Percentage of Participants Achieving Remission and Low Disease Activity According to Clinical Disease Activity Index (CDAI) at Weeks 24, 48, 72, and 96	CDAI was calculated by a simple numerical sum of tender and swollen joint count (based on 28-joint assessment) and the patient and physician global disease assessment (VAS 0-10 cm). CDAI total score 0-76; higher scores = greater effect due to disease activity. Remission was defined as CDAI score =2.8. Low disease activity was defined as CDAI score =10.0.	Weeks 24, 48, 72 and 96	No
Secondary	Change From Baseline in TJC At Weeks 24, 48, 72, and 96	68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from baseline indicated improvement.	Baseline; Weeks 24, 48, 72 and 96	No
Secondary	Change From Baseline in SJC At Weeks 24, 48, 72, and 96	66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from baseline indicated improvement.	Baseline; Weeks 24, 48, 72 and 96	No
Secondary	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96	ACR20 response: =20% improvement in TJC; =20% improvement in SJC; and =20% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; Patient Global Assessment of Disease Activity (PtGA); Physician Global Assessment of Disease Activity (PGA); self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ-DI]); and either CRP or ESR. ACR50 response required =50% improvement in the above criteria and ACR70 response required =70% improvement in the above criteria.	Weeks 24, 48, 72 and 96	No
Secondary	Change From Baseline in Hemoglobin at Weeks 20, 44, 72 and 96		Baseline; Weeks 20, 44, 72 and 96	No
Secondary	C-reactive Protein Level		Baseline; Weeks 8, 16, 24, 36 48, 72 and 96	No
Secondary	Erythrocyte Sedimentation Rate		Baseline; Weeks 8, 16, 24, 36 48, 72 and 96	No
Secondary	Participant Assessment of Pain (VAS)	The mean score of pain as assessed by participants using a 100-mm horizontal VAS, where the left endpoint (0) indicated "No pain," and the right endpoint (100) indicated "Unbearable pain". Higher score indicated higher pain.	Baseline; Weeks 8, 16, 24, 36 48, 72 and 96	No
Secondary	Change From Baseline in Health Assessment Questionnaire (HAQ) at Weeks 24, 48, 72, and 96	HAQ: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.	Baseline; Weeks 24, 48, 72 and 96	No