Clinical trial NCT02720120: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-03-25
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs)
timeFrame: Baseline up to approximately 7.25 years
measure: Percentage of Participants with Anti-Ocrelizumab Antibodies
timeFrame: Baseline up to approximately 7.25 years
Secondary outcomes:
measure: Percentage of Participants with American College of Rheumatology (ACR) 20%, 50%, and 70% (ACR20/50/70) Response at Week 24
timeFrame: Week 24
measure: Disease Activity Score at Week 24
timeFrame: Week 24
measure: Percentage of Participants achieving European League Against Rheumatism (EULAR) Response at Week 24
timeFrame: Week 24
measure: Maximum Plasma Concentration (Cmax) of Ocrelizumab
timeFrame: 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)
measure: Time to Blood B-Cell Depletion
timeFrame: Baseline up to approximately 7.25 years
measure: Terminal Elimination Half-Life (t1/2) of Ocrelizumab
timeFrame: 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)
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity AUC(0-inf) of Ocrelizumab
timeFrame: 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)
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Last Quantifiable Concentration AUC(0-last) of Ocrelizumab
timeFrame: 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)
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Ocrelizumab
timeFrame: 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)
measure: Terminal Rate Constant of Ocrelizumab
timeFrame: 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)
measure: Systemic Clearance (CL) of Ocrelizumab
timeFrame: 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)
measure: Mean Residence Time (MRT) of Ocrelizumab
timeFrame: 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)
measure: Steady State Volume of Distribution (Vss) of Ocrelizumab
timeFrame: 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)
measure: Duration of Blood B-Cell Depletion
timeFrame: Baseline up to approximately 7.25 years
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
state: New South Wales
city: Adelaide
country: Australia
state: South Australia
city: Melbourne
country: Australia
state: Victoria
city: Perth
country: Australia
state: Western Australia
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Quebec City
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
city: Amsterdam
country: Netherlands
city: Auckland City
country: New Zealand
city: Auckland
country: New Zealand
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Cádiz
country: Spain
state: Cadiz
city: Santiago de Compostela
country: Spain
state: La Coruña
city: Alcorcon
country: Spain
state: Madrid
city: La Laguna
country: Spain
state: Tenerife
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Granada
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Aberdeen
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Derby
country: United Kingdom
city: Leeds
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Maidstone
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Norwich
country: United Kingdom
city: Salford
country: United Kingdom
city: Torquay
country: United Kingdom
city: West Midlands
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: