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

This study has been terminated.
(The overall benefit risk profile of ocrelizumab was not favorable in RA)
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02720120
First received: March 22, 2016
Last updated: March 25, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: Ocrelizumab
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs) [ Time Frame: Baseline up to approximately 7.25 years ] [ Designated as safety issue: No ]
  • Percentage of Participants with Anti-Ocrelizumab Antibodies [ Time Frame: Baseline up to approximately 7.25 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants with American College of Rheumatology (ACR) 20%, 50%, and 70% (ACR20/50/70) Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Disease Activity Score at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Percentage of Participants achieving European League Against Rheumatism (EULAR) Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Time to Blood B-Cell Depletion [ Time Frame: Baseline up to approximately 7.25 years ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Duration of Blood B-Cell Depletion [ Time Frame: Baseline up to approximately 7.25 years ] [ Designated as safety issue: No ]

Enrollment: 175
Study Start Date: October 2005
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: RO4964913, rhuMAb 2H7, PRO70769

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02720120

  Show 49 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02720120     History of Changes
Other Study ID Numbers: WA18230  2004-002132-26 
Study First Received: March 22, 2016
Last Updated: March 25, 2016
Health Authority: Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on May 01, 2016