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

NCT02720120 | Terminated Phase 1

• 2 other identifiers: WA182302004-002132-26
• Study Type: interventional
• Target: 175
• Locations: 8 countries
• Sites: 49

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs)

  Baseline up to approximately 7.25 years

• Percentage of Participants with Anti-Ocrelizumab Antibodies

  Baseline up to approximately 7.25 years

Secondary Outcomes (14)

• Percentage of Participants with American College of Rheumatology (ACR) 20%, 50%, and 70% (ACR20/50/70) Response at Week 24

  Week 24

• Disease Activity Score at Week 24

  Week 24

• Percentage of Participants achieving European League Against Rheumatism (EULAR) Response at Week 24

  Week 24

• Maximum Plasma Concentration (Cmax) of Ocrelizumab

  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

  Baseline up to approximately 7.25 years

Study Arms (8)

Part 1: Ocrelizumab 1000 mg

EXPERIMENTAL

Participants will receive single IV infusion of ocrelizumab 1000 mg.

Drug: Ocrelizumab

Part 1: Ocrelizumab 1500 mg

EXPERIMENTAL

Participants will receive single IV infusion of ocrelizumab 1500 mg.

Drug: Ocrelizumab

Part 1: Ocrelizumab 2000 mg

EXPERIMENTAL

Participants will receive single IV infusion of ocrelizumab 2000 mg.

Drug: Ocrelizumab

Part 1: Ocrelizumab 400 mg

EXPERIMENTAL

Participants will receive single IV infusion of ocrelizumab 400 milligrams (mg)

Drug: Ocrelizumab

Part 1: Placebo

PLACEBO COMPARATOR

Participants will receive single IV infusion of placebo matched to ocrelizumab.

Drug: Placebo

Part 2: Ocrelizumab 1000 mg

EXPERIMENTAL

Participants will receive single IV infusion of ocrelizumab 1000 mg.

Drug: Ocrelizumab

Part 2: Ocrelizumab 1500 mg

EXPERIMENTAL

Participants will receive single IV infusion of ocrelizumab 1500 mg.

Drug: Ocrelizumab

Part 2: Ocrelizumab 400 mg

EXPERIMENTAL

Participants will receive single IV infusion of ocrelizumab 400 mg.

Drug: Ocrelizumab

Interventions

Ocrelizumab DRUG

Participants will receive single IV infusion of ocrelizumab at 400, 1000, 1500, and 2000 mg.

Also known as: RO4964913, rhuMAb 2H7, PRO70769

Part 1: Ocrelizumab 1000 mg; Part 1: Ocrelizumab 1500 mg; Part 1: Ocrelizumab 2000 mg; Part 1: Ocrelizumab 400 mg; Part 2: Ocrelizumab 1000 mg; Part 2: Ocrelizumab 1500 mg; Part 2: Ocrelizumab 400 mg

Placebo DRUG

Participants will receive single IV infusion of placebo.

Part 1: Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (49)

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Darlinghurst, New South Wales, 2010, Australia

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Adelaide, South Australia, 5041, Australia

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Melbourne, Victoria, 3004, Australia

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Perth, Western Australia, 6979, Australia

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Calgary, Alberta, T2N 4Z6, Canada

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Edmonton, Alberta, T6G 2S2, Canada

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London, Ontario, N6A 4V2, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5G 1X5, Canada

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Toronto, Ontario, M5T 2S8, Canada

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Québec, Quebec, G1V 3M7, Canada

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Sherbrooke, Quebec, J1H 5N4, Canada

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Amsterdam, 1105 AZ, Netherlands

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Auckland, 0620, New Zealand

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Auckland, 2025, New Zealand

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Moscow, 115522, Russia

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Moscow, 119049, Russia

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Moscow, 129110, Russia

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Moscow, 129327, Russia

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Saint Petersburg, 190068, Russia

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Saint Petersburg, 194291, Russia

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Saint Petersburg, 195067, Russia

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Barcelona, Barcelona, 08025, Spain

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Barcelona, Barcelona, 08035, Spain

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Cadiz, Cadiz, 11009, Spain

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Granada, Granada, 18003, Spain

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Santiago de Compostela, La Coruña, 15706, Spain

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Alcorcón, Madrid, 28922, Spain

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Madrid, Madrid, 28041, Spain

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Madrid, Madrid, 28222, Spain

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Madrid, Madrid, 28935, Spain

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Seville, Sevilla, 41014, Spain

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San Cristóbal de La Laguna, Tenerife, 38320, Spain

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Valencia, Valencia, 46017, Spain

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Aberdeen, AB25 2ZD, United Kingdom

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Cambridge, CB2 2QQ, United Kingdom

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Derby, DE22 3NE, United Kingdom

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Leeds, LS1 3EX, United Kingdom

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Liverpool, L9 7AL, United Kingdom

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London, E11 1NR, United Kingdom

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London, SE1 9RT, United Kingdom

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Maidstone, ME16 9QQ, United Kingdom

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Newcastle upon Tyne, NE1 4LP, United Kingdom

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Norwich, NR4 7UY, United Kingdom

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Salford, M6 8HD, United Kingdom

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Torquay, TQ2 7AA, United Kingdom

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West Midlands, M41 5SL, United Kingdom

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MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

ocrelizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2016
• First Posted: March 25, 2016
• Study Start: October 1, 2005
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: March 28, 2016

Record last verified: 2016-03

Locations

BE (2); CA (8); RU (7); ES (12); NZ (2); GB (13); AU (4); NL (1)