A Study to Evaluate Ocrelizumab Compared With Placebo in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy

Rheumatoid Arthritis Clinical Trial

— FEATURE  

Official title:

A Randomized, Double-Blind, Parallel-Group, International Study to Evaluate the Safety and Efficacy of Ocrelizumab Given As a Single Infusion or Dual Infusion Compared With Placebo in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00673920
• Other study ID #: ACT4394g
• Secondary ID: WA20496
• Status: Terminated
• Phase: Phase 3
• Start date: April 24, 2008
• Est. completion date: October 26, 2009

Study information

• Verified date: November 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of ocrelizumab, compared to placebo, in patients with active rheumatoid arthritis who have an inadequate response to methotrexate therapy. Patients will be randomized 2:2:1 to receive 1) infusions of ocrelizumab 200mg iv on Days 1 and 15, 2) infusions of ocrelizumab 400mg iv on Day 1 and placebo iv on Day 15, or 3) infusions of placebo iv on Days 1 and 15. At the end of the placebo-controlled treatment period at 24 weeks, patients in groups 1 and 3 will be re-randomized to receive either a single infusion of 400mg iv ocrelizumab or 2 infusions of 200mg iv ocrelizumab, and group 2 will receive a second single infusion of 400mg iv ocrelizumab. All patients will receive a stable dose of concomitant methotrexate (7.5-25mg/week) throughout the study. The anticipated time on study treatment is 1-2 years. Target number of patients to be enrolled in this trial is 300.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 314
• Est. completion date: October 26, 2009
• Est. primary completion date: October 26, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Adult patients, = 18 years of age

• Active rheumatoid arthritis

• Inadequate treatment with any DMARD other than methotrexate

Exclusion criteria:

• Rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis

• Concurrent treatment with any DMARD other than methotrexate

• Previous treatment with any cell-depleting therapies

• Any surgical procedure in past 12 weeks, or planned within 48 weeks after baseline

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Methotrexate
Oral or parenteral repeating dose
• Ocrelizumab
Ocrelizumab was administered as a slow intravenous (iv) infusion during each course as either 200 mg on Day 1 and Day 15 (OCR 200×2) or as 400 mg given on Day 1 (OCR 400×1). Ocrelizumab was administered in combination with Methotrexate.
• Placebo
Intravenous repeating dose

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Genentech, Inc.	Roche Pharma AG

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With American College of Rheumatology (ACR) 20 Response	ACR20 response: greater than or equal to (=) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale [VAS]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.	Week 24
Secondary	Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6)	The DAS28 was derived from assessments of erythrocyte sedimentation rate (ESR) measured in millimeters per hour (mm/h), tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), and Patient's Global Assessment of disease activity according to 100--millimeter (mm) Visual Analog Scale (VAS). DAS28 score was calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28 score could range from 0 to 10, where higher score represented higher disease activity. The change from Week 24 to Week 40 was averaged among all participants, where negative changes indicated an improvement in disease activity.	Week 24
Secondary	Change in DAS28 From Baseline	The DAS28 was derived from assessments of erythrocyte sedimentation rate (ESR) measured in millimeters per hour (mm/h), tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), and Patient's Global Assessment of disease activity according to 100--millimeter (mm) Visual Analog Scale (VAS). DAS28 score was calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28 score could range from 0 to 10, where higher score represented higher disease activity. The change from Week 24 to Week 40 was averaged among all participants, where negative changes indicated an improvement in disease activity. The change is the difference in adjusted mean change from baseline in DAS28 between ocrelizumab 400 x 1 and ocrelizumab 200 x 2 with placebo.	Week 24
Secondary	European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders)		Week 24
Secondary	Percentage of Participants Achieving an ACR50 Response	The ACR50 response at any time was defined as >/=50% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 50% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).	Week 24
Secondary	Percentage of Participants Achieving an ACR70 Response	The ACR70 response at any time was defined as >/=70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).	Week 24
Secondary	Change From Baseline in the Individual Parameters of the ACR Core Set	Change in the scores of the following parameters of ACR core set relative to respective baseline scores was measured: SJC (28 and 66 joints) and TJC (28 and 66 joints), patient's global assessment and physician's global assessment based on disease activity (both are expressed by VAS [0 = no disease activity to 100 = maximum disease activity]), HAQ (based on HAQ disability index [HAQDI]) which included 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do), where the sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst), pain assessment using a VAS ranging from score 0 (no pain) to 100 (unbearable pain).	Week 24
Secondary	Change From Baseline in the Individual Parameters of the ACR Core Set: C-Reactive Protein (CRP) Concentration		Week 24
Secondary	Change From Baseline in the Individual Parameters of the ACR Core Set: Erythrocyte Sedimentation Rate (ESR)		Week 24
Secondary	Percentage of Participants With a Reduction of Greater Than or Equal to 0.25 Units in the HAQ-DI Score		Week 24
Secondary	Change in SF-36 Subscale and Summary Scores From Baseline	Improved, change > 5.42; Unchanged, -5.42 <= Change <= 5.42; Worsened, change < -5.42	Week 24
Secondary	Change in FACIT-F Fatigue Assessment From Baseline	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. FACIT-F is a 13-item questionnaire. 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 participants 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 (worse score) to 52 (better score). Clinically relevant improvement is defined as a greater than or equal to (=)5-point change from Baseline.	Baseline, Weeks 4, 12, and 24
Secondary	Percentage of Participants Achieving an ACR20 Response	ACR20 response: greater than or equal to (=) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale [VAS]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.	Week 48
Secondary	Percentage of Participants Achieving an ACR50 Response	The ACR50 response at any time was defined as >/=50% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 50% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).	Week 48
Secondary	Percentage of Participants Achieving an ACR70 Response	The ACR70 response at any time was defined as >/=70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).	Week 48
Secondary	Percentage of Participants Achieving DAS28 Remission (DAS28 < 2.6)		Week 48
Secondary	Cmax: Maximum Observed Serum Concentration of Ocrelizumab Following First Infusion		Week 24, 48
Secondary	Csecond: Maximum Observed Serum Concentration of Ocrelizumab Following Second Infusion		Day 15 of Cycles 1 and 2