A Study of Ocrelizumab in Participants With Moderate to Severe Rheumatoid Arthritis (RA)

March 25, 2016 updated by: Hoffmann-La Roche

A Randomized Placebo-Controlled, Multi-Center, Phase I/II Study of the Safety of Escalating Single Intravenous Doses of Ocrelizumab (rhuMAb 2H7, RO4964913, PRO70769) in Patients With Moderate to Severe Rheumatoid Arthritis Receiving Stable Doses of Concomitant Methotrexate But With Unsatisfactory Clinical Response

This study is in two parts and will evaluate the safety, tolerability and efficacy of escalating single intravenous (IV) doses of ocrelizumab compared with placebo in combination with methotrexate in participants with moderate to severe RA. Part 1 is the dose-escalation study, at one of the following dose levels of ocrelizumab [400, 1000, 1500, and 2000 milligrams (mg)]. In Part 2, participants will be randomized to explore tolerability and efficacy of doses which have been shown to be tolerated in Part 1.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
175

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
    • South Australia
      • Adelaide, South Australia, Australia, 5041
    • Victoria
      • Melbourne, Victoria, Australia, 3004
    • Western Australia
      • Perth, Western Australia, Australia, 6979
  • Belgium
      • Gent, Belgium, 9000
      • Leuven, Belgium, 3000
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
      • Edmonton, Alberta, Canada, T6G 2S2
    • Ontario
      • London, Ontario, Canada, N6A 4V2
      • Toronto, Ontario, Canada, M5T 2S8
      • Toronto, Ontario, Canada, M4N 3M5
      • Toronto, Ontario, Canada, M5G 1X5
    • Quebec
      • Quebec City, Quebec, Canada, G1V 3M7
      • Sherbrooke, Quebec, Canada, J1H 5N4
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
  • New Zealand
      • Auckland, New Zealand, 2025
      • Auckland City, New Zealand, 0620
  • Russian Federation
      • Moscow, Russian Federation, 115522
      • Moscow, Russian Federation, 119049
      • Moscow, Russian Federation, 129110
      • Moscow, Russian Federation, 129327
      • Saint-Petersburg, Russian Federation, 195067
      • St Petersburg, Russian Federation, 194291
      • St. Petersburg, Russian Federation, 190068
  • Spain
      • Barcelona, Spain, 08035
      • Barcelona, Spain, 08025
      • Granada, Spain, 18003
      • Madrid, Spain, 28041
      • Madrid, Spain, 28222
      • Madrid, Spain, 28935
      • Sevilla, Spain, 41014
      • Valencia, Spain, 46017
    • Cadiz
      • Cádiz, Cadiz, Spain, 11009
    • La Coruña
      • Santiago de Compostela, La Coruña, Spain, 15706
    • Madrid
      • Alcorcon, Madrid, Spain, 28922
    • Tenerife
      • La Laguna, Tenerife, Spain, 38320
  • United Kingdom
      • Aberdeen, United Kingdom, AB25 2ZD
      • Cambridge, United Kingdom, CB2 2QQ
      • Derby, United Kingdom, DE22 3NE
      • Leeds, United Kingdom, LS1 3EX
      • Liverpool, United Kingdom, L9 7AL
      • London, United Kingdom, E11 1NR
      • London, United Kingdom, SE1 9RT
      • Maidstone, United Kingdom, ME16 9QQ
      • Newcastle Upon Tyne, United Kingdom, NE1 4LP
      • Norwich, United Kingdom, NR4 7UY
      • Salford, United Kingdom, M6 8HD
      • Torquay, United Kingdom, TQ2 7AA
      • West Midlands, United Kingdom, M41 5SL

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Moderate to severe RA for at least 6 months
  • Positive serum rheumatoid factor (>/= 20 international units per milliliter)
  • Current treatment with RA on an outpatient basis
  • Treatment failure with one disease modifying anti-rheumatic drug (DMARD) or biologic, but have not failed more than six of these agents including methotrexate
  • Current treatment with methotrexate for at least 12 weeks, at a stable dose
  • Use of highly effective contraception.

Exclusion Criteria:

  • Rheumatic autoimmune disease or inflammatory joint disease, other than RA
  • Concurrent treatment with any disease-modifying anti-rheumatic drug (DMARD) (other than methotrexate) or any anti-tumor necrosis factor (TNF) -alfa or other biologic therapy
  • Treatment with any other investigational drug within 4 weeks of screening
  • Previous treatment with cell-depleting therapies, IV gamma-globulin, intra-articular or parenteral corticosteroids, and receipt of live/attenuated vaccine prior to screening
  • Previous treatment with rituximab or any other anti-cluster of differentiation 20 (CD20) agent
  • History of severe allergic or anaphylactic reactions to humanized monoclonal antibodies
  • Known active bacterial, viral or fungal infections
  • History of active tuberculosis and primary or secondary immunodeficiency
  • History of concomitant diseases such as cardiovascular disease, nervous system, pulmonary disease, renal, hepatic, endocrine or gastrointestinal disorders
  • Pregnancy or lactation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part 1: Ocrelizumab 1000 mg
Participants will receive single IV infusion of ocrelizumab 1000 mg.
Drug: Ocrelizumab
Participants will receive single IV infusion of ocrelizumab at 400, 1000, 1500, and 2000 mg.
Other Names:
  • RO4964913, rhuMAb 2H7, PRO70769
Experimental: Part 1: Ocrelizumab 1500 mg
Participants will receive single IV infusion of ocrelizumab 1500 mg.
Drug: Ocrelizumab
Participants will receive single IV infusion of ocrelizumab at 400, 1000, 1500, and 2000 mg.
Other Names:
  • RO4964913, rhuMAb 2H7, PRO70769
Experimental: Part 1: Ocrelizumab 2000 mg
Participants will receive single IV infusion of ocrelizumab 2000 mg.
Drug: Ocrelizumab
Participants will receive single IV infusion of ocrelizumab at 400, 1000, 1500, and 2000 mg.
Other Names:
  • RO4964913, rhuMAb 2H7, PRO70769
Experimental: Part 1: Ocrelizumab 400 mg
Participants will receive single IV infusion of ocrelizumab 400 milligrams (mg)
Drug: Ocrelizumab
Participants will receive single IV infusion of ocrelizumab at 400, 1000, 1500, and 2000 mg.
Other Names:
  • RO4964913, rhuMAb 2H7, PRO70769
Placebo Comparator: Part 1: Placebo
Participants will receive single IV infusion of placebo matched to ocrelizumab.
Drug: Placebo
Participants will receive single IV infusion of placebo.
Experimental: Part 2: Ocrelizumab 1000 mg
Participants will receive single IV infusion of ocrelizumab 1000 mg.
Drug: Ocrelizumab
Participants will receive single IV infusion of ocrelizumab at 400, 1000, 1500, and 2000 mg.
Other Names:
  • RO4964913, rhuMAb 2H7, PRO70769
Experimental: Part 2: Ocrelizumab 1500 mg
Participants will receive single IV infusion of ocrelizumab 1500 mg.
Drug: Ocrelizumab
Participants will receive single IV infusion of ocrelizumab at 400, 1000, 1500, and 2000 mg.
Other Names:
  • RO4964913, rhuMAb 2H7, PRO70769
Experimental: Part 2: Ocrelizumab 400 mg
Participants will receive single IV infusion of ocrelizumab 400 mg.
Drug: Ocrelizumab
Participants will receive single IV infusion of ocrelizumab at 400, 1000, 1500, and 2000 mg.
Other Names:
  • RO4964913, rhuMAb 2H7, PRO70769

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs)
Time Frame: Baseline up to approximately 7.25 years
Baseline up to approximately 7.25 years
Percentage of Participants with Anti-Ocrelizumab Antibodies
Time Frame: Baseline up to approximately 7.25 years
Baseline up to approximately 7.25 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Percentage of Participants with American College of Rheumatology (ACR) 20%, 50%, and 70% (ACR20/50/70) Response at Week 24
Time Frame: Week 24
Week 24
Disease Activity Score at Week 24
Time Frame: Week 24
Week 24
Percentage of Participants achieving European League Against Rheumatism (EULAR) Response at Week 24
Time Frame: Week 24
Week 24
Maximum Plasma Concentration (Cmax) of Ocrelizumab
Time Frame: Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Time to Blood B-Cell Depletion
Time Frame: Baseline up to approximately 7.25 years
Baseline up to approximately 7.25 years
Terminal Elimination Half-Life (t1/2) of Ocrelizumab
Time Frame: Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity AUC(0-inf) of Ocrelizumab
Time Frame: Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Quantifiable Concentration AUC(0-last) of Ocrelizumab
Time Frame: Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Time to Maximum Observed Plasma Concentration (Tmax) of Ocrelizumab
Time Frame: Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Terminal Rate Constant of Ocrelizumab
Time Frame: Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Systemic Clearance (CL) of Ocrelizumab
Time Frame: Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Mean Residence Time (MRT) of Ocrelizumab
Time Frame: Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Steady State Volume of Distribution (Vss) of Ocrelizumab
Time Frame: Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24)
Duration of Blood B-Cell Depletion
Time Frame: Baseline up to approximately 7.25 years
Baseline up to approximately 7.25 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2005

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 22, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 25, 2016

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 28, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • WA18230
  • 2004-002132-26 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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