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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02720120
• Other study ID #: WA18230
• Secondary ID: 2004-002132-26
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: March 22, 2016
• Last updated: March 25, 2016
• Start date: October 2005
• Est. completion date: February 2013

Study information

• Verified date: March 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 175
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Ocrelizumab
Participants will receive single IV infusion of ocrelizumab at 400, 1000, 1500, and 2000 mg.
• Placebo
Participants will receive single IV infusion of placebo.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  Netherlands,  New Zealand,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs)		Baseline up to approximately 7.25 years	No
Primary	Percentage of Participants with Anti-Ocrelizumab Antibodies		Baseline up to approximately 7.25 years	No
Secondary	Percentage of Participants with American College of Rheumatology (ACR) 20%, 50%, and 70% (ACR20/50/70) Response at Week 24		Week 24	No
Secondary	Disease Activity Score at Week 24		Week 24	No
Secondary	Percentage of Participants achieving European League Against Rheumatism (EULAR) Response at Week 24		Week 24	No
Secondary	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)	No
Secondary	Time to Blood B-Cell Depletion		Baseline up to approximately 7.25 years	No
Secondary	Terminal Elimination Half-Life (t1/2) 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)	No
Secondary	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity AUC(0-inf) 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)	No
Secondary	Area Under the Plasma Concentration-Time Curve From Time 0 to Last Quantifiable Concentration AUC(0-last) 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)	No
Secondary	Time to Maximum Observed Plasma Concentration (Tmax) 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)	No
Secondary	Terminal Rate Constant 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)	No
Secondary	Systemic Clearance (CL) 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)	No
Secondary	Mean Residence Time (MRT) 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)	No
Secondary	Steady State Volume of Distribution (Vss) 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)	No
Secondary	Duration of Blood B-Cell Depletion		Baseline up to approximately 7.25 years	No