Back to resultsA Study of Ocrelizumab in Participants With Moderate to Severe Rheumatoid Arthritis (RA)
Primary Purpose
Rheumatoid Arthritis
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Ocrelizumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Part 1: Ocrelizumab 1000 mg
Part 1: Ocrelizumab 1500 mg
Part 1: Ocrelizumab 2000 mg
Part 1: Ocrelizumab 400 mg
Part 1: Placebo
Part 2: Ocrelizumab 1000 mg
Part 2: Ocrelizumab 1500 mg
Part 2: Ocrelizumab 400 mg
Arm Description
Participants will receive single IV infusion of ocrelizumab 1000 mg.
Participants will receive single IV infusion of ocrelizumab 1500 mg.
Participants will receive single IV infusion of ocrelizumab 2000 mg.
Participants will receive single IV infusion of ocrelizumab 400 milligrams (mg)
Participants will receive single IV infusion of placebo matched to ocrelizumab.
Participants will receive single IV infusion of ocrelizumab 1000 mg.
Participants will receive single IV infusion of ocrelizumab 1500 mg.
Participants will receive single IV infusion of ocrelizumab 400 mg.
Outcomes
Primary Outcome Measures
Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs)
Percentage of Participants with Anti-Ocrelizumab Antibodies
Secondary Outcome Measures
Percentage of Participants with American College of Rheumatology (ACR) 20%, 50%, and 70% (ACR20/50/70) Response at Week 24
Disease Activity Score at Week 24
Percentage of Participants achieving European League Against Rheumatism (EULAR) Response at Week 24
Maximum Plasma Concentration (Cmax) of Ocrelizumab
Time to Blood B-Cell Depletion
Terminal Elimination Half-Life (t1/2) of Ocrelizumab
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity AUC(0-inf) of Ocrelizumab
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Quantifiable Concentration AUC(0-last) of Ocrelizumab
Time to Maximum Observed Plasma Concentration (Tmax) of Ocrelizumab
Terminal Rate Constant of Ocrelizumab
Systemic Clearance (CL) of Ocrelizumab
Mean Residence Time (MRT) of Ocrelizumab
Steady State Volume of Distribution (Vss) of Ocrelizumab
Duration of Blood B-Cell Depletion
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02720120
Brief Title
A Study of Ocrelizumab in Participants With Moderate to Severe Rheumatoid Arthritis (RA)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Terminated
Why Stopped
The overall benefit risk profile of ocrelizumab was not favorable in RA
Study Start Date
October 2005 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
175 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1: Ocrelizumab 1000 mg
Arm Type
Experimental
Arm Description
Participants will receive single IV infusion of ocrelizumab 1000 mg.
Arm Title
Part 1: Ocrelizumab 1500 mg
Arm Type
Experimental
Arm Description
Participants will receive single IV infusion of ocrelizumab 1500 mg.
Arm Title
Part 1: Ocrelizumab 2000 mg
Arm Type
Experimental
Arm Description
Participants will receive single IV infusion of ocrelizumab 2000 mg.
Arm Title
Part 1: Ocrelizumab 400 mg
Arm Type
Experimental
Arm Description
Participants will receive single IV infusion of ocrelizumab 400 milligrams (mg)
Arm Title
Part 1: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive single IV infusion of placebo matched to ocrelizumab.
Arm Title
Part 2: Ocrelizumab 1000 mg
Arm Type
Experimental
Arm Description
Participants will receive single IV infusion of ocrelizumab 1000 mg.
Arm Title
Part 2: Ocrelizumab 1500 mg
Arm Type
Experimental
Arm Description
Participants will receive single IV infusion of ocrelizumab 1500 mg.
Arm Title
Part 2: Ocrelizumab 400 mg
Arm Type
Experimental
Arm Description
Participants will receive single IV infusion of ocrelizumab 400 mg.
Intervention Type
Drug
Intervention Name(s)
Ocrelizumab
Other Intervention Name(s)
RO4964913, rhuMAb 2H7, PRO70769
Intervention Description
Participants will receive single IV infusion of ocrelizumab at 400, 1000, 1500, and 2000 mg.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive single IV infusion of placebo.
Primary Outcome Measure Information:
Title
Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs)
Time Frame
Baseline up to approximately 7.25 years
Title
Percentage of Participants with Anti-Ocrelizumab Antibodies
Time Frame
Baseline up to approximately 7.25 years
Secondary Outcome Measure Information:
Title
Percentage of Participants with American College of Rheumatology (ACR) 20%, 50%, and 70% (ACR20/50/70) Response at Week 24
Time Frame
Week 24
Title
Disease Activity Score at Week 24
Time Frame
Week 24
Title
Percentage of Participants achieving European League Against Rheumatism (EULAR) Response at Week 24
Time Frame
Week 24
Title
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)
Title
Time to Blood B-Cell Depletion
Time Frame
Baseline up to approximately 7.25 years
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
Duration of Blood B-Cell Depletion
Time Frame
Baseline up to approximately 7.25 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5041
Country
Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6979
Country
Australia
City
Gent
ZIP/Postal Code
9000
Country
Belgium
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2S2
Country
Canada
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4V2
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X5
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1V 3M7
Country
Canada
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
City
Auckland City
ZIP/Postal Code
0620
Country
New Zealand
City
Auckland
ZIP/Postal Code
2025
Country
New Zealand
City
Moscow
ZIP/Postal Code
115522
Country
Russian Federation
City
Moscow
ZIP/Postal Code
119049
Country
Russian Federation
City
Moscow
ZIP/Postal Code
129110
Country
Russian Federation
City
Moscow
ZIP/Postal Code
129327
Country
Russian Federation
City
Saint-Petersburg
ZIP/Postal Code
195067
Country
Russian Federation
City
St Petersburg
ZIP/Postal Code
194291
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
190068
Country
Russian Federation
City
Cádiz
State/Province
Cadiz
ZIP/Postal Code
11009
Country
Spain
City
Santiago de Compostela
State/Province
La Coruña
ZIP/Postal Code
15706
Country
Spain
City
Alcorcon
State/Province
Madrid
ZIP/Postal Code
28922
Country
Spain
City
La Laguna
State/Province
Tenerife
ZIP/Postal Code
38320
Country
Spain
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Granada
ZIP/Postal Code
18003
Country
Spain
City
Madrid
ZIP/Postal Code
28041
Country
Spain
City
Madrid
ZIP/Postal Code
28222
Country
Spain
City
Madrid
ZIP/Postal Code
28935
Country
Spain
City
Sevilla
ZIP/Postal Code
41014
Country
Spain
City
Valencia
ZIP/Postal Code
46017
Country
Spain
City
Aberdeen
ZIP/Postal Code
AB25 2ZD
Country
United Kingdom
City
Cambridge
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
City
Derby
ZIP/Postal Code
DE22 3NE
Country
United Kingdom
City
Leeds
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
City
Liverpool
ZIP/Postal Code
L9 7AL
Country
United Kingdom
City
London
ZIP/Postal Code
E11 1NR
Country
United Kingdom
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
City
Maidstone
ZIP/Postal Code
ME16 9QQ
Country
United Kingdom
City
Newcastle Upon Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
City
Norwich
ZIP/Postal Code
NR4 7UY
Country
United Kingdom
City
Salford
ZIP/Postal Code
M6 8HD
Country
United Kingdom
City
Torquay
ZIP/Postal Code
TQ2 7AA
Country
United Kingdom
City
West Midlands
ZIP/Postal Code
M41 5SL
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of Ocrelizumab in Participants With Moderate to Severe Rheumatoid Arthritis (RA)
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