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A Study to Evaluate Ocrelizumab in Combination With Methotrexate Compared With Infliximab Plus Methotrexate in Patients With Active Rheumatoid Arthritis Currently Responding Inadequately to Etanercept or Adalimumab

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ClinicalTrials.gov Identifier: NCT00808210
Recruitment Status : Terminated (Based on analysis of results and consideration of available treatments, the overall benefit to risk profile of ocrelizumab was not favorable in RA.)
First Posted : December 15, 2008
Results First Posted : November 6, 2020
Last Update Posted : November 6, 2020
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: Infliximab
Drug: Methotrexate
Drug: Methylprednisolone
Drug: Ocrelizumab
Drug: Placebo
Enrollment 28
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ocrelizumab 200mg Infliximab 5mg/kg
Hide Arm/Group Description Participants received two intravenous (IV) infusions of 200 mg ocrelizumab administered on Day 1 and Day 15 and placebo IV infliximab infusions administered on Day 1, Day 15, Week 6, and Week 14. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity. Participants received four IV infusions of 5 mg/kg infliximab administered on Day 1, Day 15, Week 6, and Week 14 and placebo ocrelizumab infusions administered on Day 1 and Day 15. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Period Title: Study Period + 48 Weeks of Follow-up
Started 15 13
Completed 6 4
Not Completed 9 9
Reason Not Completed
Sponsor decision to terminate study             3             7
Other reasons outside Sponsor decision             6             2
Period Title: Double-Blind TX Period
Started 15 13
Completed 13 10
Not Completed 2 3
Reason Not Completed
Adverse Event             0             1
Sponsor decision to terminate study             1             1
Other reasons outside Sponsor decision             1             1
Period Title: Open Label Ocrelizumab Treatment Period
Started 9 4
Completed 0 0
Not Completed 9 4
Reason Not Completed
Sponsor decision to terminate study             9             4
Arm/Group Title Ocrelizumab 200mg Infliximab 5mg/kg Total
Hide Arm/Group Description Participants received two intravenous (IV) infusions of 200 mg ocrelizumab administered on Day 1 and Day 15 and placebo IV infliximab infusions administered on Day 1, Day 15, Week 6, and Week 14. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity. Participants received four IV infusions of 5 mg/kg infliximab administered on Day 1, Day 15, Week 6, and Week 14 and placebo ocrelizumab infusions administered on Day 1 and Day 15. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity. Total of all reporting groups
Overall Number of Baseline Participants 15 13 28
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 13 participants 28 participants
53.5  (12.9) 54.2  (15.2) 53.83  (13.97)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 13 participants 28 participants
Female
6
  40.0%
10
  76.9%
16
  57.1%
Male
9
  60.0%
3
  23.1%
12
  42.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 13 participants 28 participants
Hispanic or Latino
1
   6.7%
1
   7.7%
2
   7.1%
Not Hispanic or Latino
14
  93.3%
12
  92.3%
26
  92.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 13 participants 28 participants
American Indian or Alaska Native
1
   6.7%
0
   0.0%
1
   3.6%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  13.3%
4
  30.8%
6
  21.4%
White
12
  80.0%
9
  69.2%
21
  75.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change From Baseline in DAS28(ESR) at Week 20
Hide Description [Not Specified]
Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The study was terminated before data for the primary and secondary efficacy endpoints were collected so no data was collected for these efficacy endpoints.
Arm/Group Title Ocrelizumab 200mg Infliximab 5mg/kg
Hide Arm/Group Description:
Participants received two intravenous (IV) infusions of 200 mg ocrelizumab administered on Day 1 and Day 15 and placebo IV infliximab infusions administered on Day 1, Day 15, Week 6, and Week 14. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Participants received four IV infusions of 5 mg/kg infliximab administered on Day 1, Day 15, Week 6, and Week 14 and placebo ocrelizumab infusions administered on Day 1 and Day 15. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Percentage of Participants With Clinical Response of 20% According to ACR Criteria
Hide Description [Not Specified]
Time Frame Baseline up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
The study was terminated before data for the primary and secondary efficacy endpoints were collected so no data was collected for these efficacy endpoints.
Arm/Group Title Ocrelizumab 200mg Infliximab 5mg/kg
Hide Arm/Group Description:
Participants received two intravenous (IV) infusions of 200 mg ocrelizumab administered on Day 1 and Day 15 and placebo IV infliximab infusions administered on Day 1, Day 15, Week 6, and Week 14. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Participants received four IV infusions of 5 mg/kg infliximab administered on Day 1, Day 15, Week 6, and Week 14 and placebo ocrelizumab infusions administered on Day 1 and Day 15. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Percentage of Participants With Clinical Response of 50% According to ACR Criteria
Hide Description [Not Specified]
Time Frame Baseline up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
The study was terminated before data for the primary and secondary efficacy endpoints were collected so no data was collected for these efficacy endpoints.
Arm/Group Title Ocrelizumab 200mg Infliximab 5mg/kg
Hide Arm/Group Description:
Participants received two intravenous (IV) infusions of 200 mg ocrelizumab administered on Day 1 and Day 15 and placebo IV infliximab infusions administered on Day 1, Day 15, Week 6, and Week 14. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Participants received four IV infusions of 5 mg/kg infliximab administered on Day 1, Day 15, Week 6, and Week 14 and placebo ocrelizumab infusions administered on Day 1 and Day 15. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Percentage of Participants With Clinical Response of 70% According to ACR Criteria
Hide Description [Not Specified]
Time Frame Baseline up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
The study was terminated before data for the primary and secondary efficacy endpoints were collected so no data was collected for these efficacy endpoints.
Arm/Group Title Ocrelizumab 200mg Infliximab 5mg/kg
Hide Arm/Group Description:
Participants received two intravenous (IV) infusions of 200 mg ocrelizumab administered on Day 1 and Day 15 and placebo IV infliximab infusions administered on Day 1, Day 15, Week 6, and Week 14. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Participants received four IV infusions of 5 mg/kg infliximab administered on Day 1, Day 15, Week 6, and Week 14 and placebo ocrelizumab infusions administered on Day 1 and Day 15. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title European League Against Rheumatism (EULAR) Response Rates
Hide Description [Not Specified]
Time Frame Baseline up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
The study was terminated before data for the primary and secondary efficacy endpoints were collected so no data was collected for these efficacy endpoints.
Arm/Group Title Ocrelizumab 200mg Infliximab 5mg/kg
Hide Arm/Group Description:
Participants received two intravenous (IV) infusions of 200 mg ocrelizumab administered on Day 1 and Day 15 and placebo IV infliximab infusions administered on Day 1, Day 15, Week 6, and Week 14. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Participants received four IV infusions of 5 mg/kg infliximab administered on Day 1, Day 15, Week 6, and Week 14 and placebo ocrelizumab infusions administered on Day 1 and Day 15. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Hide Description [Not Specified]
Time Frame Baseline up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
The study was terminated before data for the primary and secondary efficacy endpoints were collected so no data was collected for these efficacy endpoints.
Arm/Group Title Ocrelizumab 200mg Infliximab 5mg/kg
Hide Arm/Group Description:
Participants received two intravenous (IV) infusions of 200 mg ocrelizumab administered on Day 1 and Day 15 and placebo IV infliximab infusions administered on Day 1, Day 15, Week 6, and Week 14. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Participants received four IV infusions of 5 mg/kg infliximab administered on Day 1, Day 15, Week 6, and Week 14 and placebo ocrelizumab infusions administered on Day 1 and Day 15. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Change in Fatigue Visual Analog Scale Score (VAS)
Hide Description [Not Specified]
Time Frame Baseline up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
The study was terminated before data for the primary and secondary efficacy endpoints were collected so no data was collected for these efficacy endpoints.
Arm/Group Title Ocrelizumab 200mg Infliximab 5mg/kg
Hide Arm/Group Description:
Participants received two intravenous (IV) infusions of 200 mg ocrelizumab administered on Day 1 and Day 15 and placebo IV infliximab infusions administered on Day 1, Day 15, Week 6, and Week 14. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Participants received four IV infusions of 5 mg/kg infliximab administered on Day 1, Day 15, Week 6, and Week 14 and placebo ocrelizumab infusions administered on Day 1 and Day 15. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Percentage of Participants With Adverse Events (AEs)
Hide Description [Not Specified]
Time Frame Baseline up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ocrelizumab 200mg Infliximab 5mg/kg
Hide Arm/Group Description:
Participants received two intravenous (IV) infusions of 200 mg ocrelizumab administered on Day 1 and Day 15 and placebo IV infliximab infusions administered on Day 1, Day 15, Week 6, and Week 14. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Participants received four IV infusions of 5 mg/kg infliximab administered on Day 1, Day 15, Week 6, and Week 14 and placebo ocrelizumab infusions administered on Day 1 and Day 15. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
Overall Number of Participants Analyzed 15 13
Measure Type: Number
Unit of Measure: Percentage of Participants
78.9 76.9
Time Frame Baseline up to 43 months
Adverse Event Reporting Description 4 patients from infliximab switched to ocrelizumab during the open label phase and the summary of AEs were summarized in the ocrelizumab arm for the safety analysis.
 
Arm/Group Title Ocrelizumab 200mg Infliximab 5mg/kg
Hide Arm/Group Description Participants received two intravenous (IV) infusions of 200 mg ocrelizumab administered on Day 1 and Day 15 and placebo IV infliximab infusions administered on Day 1, Day 15, Week 6, and Week 14. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity. Participants received four IV infusions of 5 mg/kg infliximab administered on Day 1, Day 15, Week 6, and Week 14 and placebo ocrelizumab infusions administered on Day 1 and Day 15. In addition to the study medication, all patients were to receive methotrexate at a stable dose of 7.5-25 mg/week and folic acid or equivalent at a dose of 5 mg/week to minimize methotrexate toxicity.
All-Cause Mortality
Ocrelizumab 200mg Infliximab 5mg/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)      0/13 (0.00%)    
Hide Serious Adverse Events
Ocrelizumab 200mg Infliximab 5mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/19 (10.53%)      0/13 (0.00%)    
Gastrointestinal disorders     
ENTERITIS  1  1/19 (5.26%)  1 0/13 (0.00%)  0
GASTROINTESTINAL HAEMORRHAGE  1  1/19 (5.26%)  1 0/13 (0.00%)  0
Musculoskeletal and connective tissue disorders     
HUMERUS FRACTURE  1  1/19 (5.26%)  1 0/13 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE  1  1/19 (5.26%)  1 0/13 (0.00%)  0
RESPIRATORY FAILURE  1  1/19 (5.26%)  1 0/13 (0.00%)  0
1
Term from vocabulary, MedDRA v15.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0.05%
Ocrelizumab 200mg Infliximab 5mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/19 (78.95%)      10/13 (76.92%)    
Gastrointestinal disorders     
NAUSEA  1  2/19 (10.53%)  2 2/13 (15.38%)  2
DIARRHOEA  1  2/19 (10.53%)  2 1/13 (7.69%)  1
VOMITING  1  1/19 (5.26%)  1 1/13 (7.69%)  1
ABDOMINAL DISCOMFORT  1  1/19 (5.26%)  1 0/13 (0.00%)  0
DYSPEPSIA  1  0/19 (0.00%)  0 1/13 (7.69%)  1
ENTERITIS  1  1/19 (5.26%)  1 0/13 (0.00%)  0
GASTROINTESTINAL HAEMORRHAGE  1  1/19 (5.26%)  1 0/13 (0.00%)  0
GASTROOESOPHAGEAL REFLUX DISEASE  1  1/19 (5.26%)  1 0/13 (0.00%)  0
TOOTHACHE  1  1/19 (5.26%)  1 0/13 (0.00%)  0
General disorders     
CHILLS  1  1/19 (5.26%)  1 2/13 (15.38%)  2
FATIGUE  1  0/19 (0.00%)  0 1/13 (7.69%)  1
CHEST PAIN  1  1/19 (5.26%)  1 1/13 (7.69%)  1
OEDEMA PERIPHERAL  1  0/19 (0.00%)  0 1/13 (7.69%)  1
Hepatobiliary disorders     
CHOLELITHIASIS  1  1/19 (5.26%)  1 0/13 (0.00%)  0
Infections and infestations     
UPPER RESPIRATORY TRACT INFECTIOn  1  4/19 (21.05%)  4 1/13 (7.69%)  1
SINUSITIS  1  3/19 (15.79%)  3 0/13 (0.00%)  0
ALVEOLAR OSTEITIS  1  1/19 (5.26%)  1 0/13 (0.00%)  0
BRONCHITIS  1  1/19 (5.26%)  1 0/13 (0.00%)  0
CYSTITIS  1  0/19 (0.00%)  0 1/13 (7.69%)  1
HERPES ZOSTER  1  2/19 (10.53%)  2 0/13 (0.00%)  0
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE  1  1/19 (5.26%)  1 0/13 (0.00%)  0
INFLUENZA  1  0/19 (0.00%)  0 1/13 (7.69%)  1
ORAL CANDIDIASIS  1  1/19 (5.26%)  1 0/13 (0.00%)  0
ORAL INFECTION  1  1/19 (5.26%)  1 0/13 (0.00%)  0
SKIN INFECTION  1  1/19 (5.26%)  1 0/13 (0.00%)  0
TOOTH ABSCESS  1  1/19 (5.26%)  1 0/13 (0.00%)  0
URINARY TRACT INFECTION  1  0/19 (0.00%)  0 1/13 (7.69%)  1
Investigations     
HEART RATE INCREASED  1  0/19 (0.00%)  0 1/13 (7.69%)  1
Metabolism and nutrition disorders     
DIABETES MELLITUS  1  0/19 (0.00%)  0 1/13 (7.69%)  1
Musculoskeletal and connective tissue disorders     
RHEUMATOID ARTHRITIS  1  0/19 (0.00%)  0 3/13 (23.08%)  3
ARTHRALGIA  1  1/19 (5.26%)  1 1/13 (7.69%)  1
FIBROMYALGIA  1  1/19 (5.26%)  1 1/13 (7.69%)  1
PAIN IN EXTREMITY  1  0/19 (0.00%)  0 1/13 (7.69%)  1
PATHOLOGICAL FRACTURE  1  1/19 (5.26%)  1 0/13 (0.00%)  0
JOINT DISLOCATION  1  1/19 (5.26%)  1 0/13 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
BENIGN NEOPLASM OF THYROID GLAND  1  1/19 (5.26%)  1 0/13 (0.00%)  0
Nervous system disorders     
HEADACHE  1  0/19 (0.00%)  0 2/13 (15.38%)  2
CARPAL TUNNEL SYNDROME  1  0/19 (0.00%)  0 1/13 (7.69%)  1
HEAD TITUBATION  1  0/19 (0.00%)  0 1/13 (7.69%)  1
RESTLESS LEGS SYNDROME  1  1/19 (5.26%)  1 0/13 (0.00%)  0
Skin and subcutaneous tissue disorders     
RASH  1  3/19 (15.79%)  3 0/13 (0.00%)  0
COLD SWEAT  1  0/19 (0.00%)  0 1/13 (7.69%)  1
DERMATITIS CONTACT  1  1/19 (5.26%)  1 0/13 (0.00%)  0
HYPERHIDROSIS  1  0/19 (0.00%)  0 1/13 (7.69%)  1
PRURITUS  1  1/19 (5.26%)  1 0/13 (0.00%)  0
ROSACEA  1  0/19 (0.00%)  0 1/13 (7.69%)  1
Surgical and medical procedures     
TOOTH EXTRACTION  1  1/19 (5.26%)  1 0/13 (0.00%)  0
Vascular disorders     
HYPERTENSION  1  0/19 (0.00%)  0 1/13 (7.69%)  1
1
Term from vocabulary, MedDRA v15.1
Indicates events were collected by systematic assessment
At the time of study termination the scope of the statistical analyses was reduced and limited to evaluation of the safety profile.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: F. Hoffmann-La Roche Ltd
Phone: +41 616878333
EMail: global.trial_information@roche.com
Layout table for additonal information
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00808210    
Other Study ID Numbers: ACT4562g
GA00931
First Submitted: December 11, 2008
First Posted: December 15, 2008
Results First Submitted: August 27, 2020
Results First Posted: November 6, 2020
Last Update Posted: November 6, 2020