Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02720120




Registration number
NCT02720120
Ethics application status
Date submitted
22/03/2016
Date registered
25/03/2016
Date last updated
28/03/2016

Titles & IDs
Public title
A Study of Ocrelizumab in Participants With Moderate to Severe Rheumatoid Arthritis (RA)
Scientific 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
Secondary ID [1] 0 0
2004-002132-26
Secondary ID [2] 0 0
WA18230
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ocrelizumab
Treatment: Drugs - Placebo

Experimental: Part 1: Ocrelizumab 1000 mg - Participants will receive single IV infusion of ocrelizumab 1000 mg.

Experimental: Part 1: Ocrelizumab 1500 mg - Participants will receive single IV infusion of ocrelizumab 1500 mg.

Experimental: Part 1: Ocrelizumab 2000 mg - Participants will receive single IV infusion of ocrelizumab 2000 mg.

Experimental: Part 1: Ocrelizumab 400 mg - Participants will receive single IV infusion of ocrelizumab 400 milligrams (mg)

Placebo Comparator: Part 1: Placebo - Participants will receive single IV infusion of placebo matched to ocrelizumab.

Experimental: Part 2: Ocrelizumab 1000 mg - Participants will receive single IV infusion of ocrelizumab 1000 mg.

Experimental: Part 2: Ocrelizumab 1500 mg - Participants will receive single IV infusion of ocrelizumab 1500 mg.

Experimental: Part 2: Ocrelizumab 400 mg - Participants will receive single IV infusion of ocrelizumab 400 mg.


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

Treatment: Drugs: Placebo
Participants will receive single IV infusion of placebo.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs)
Timepoint [1] 0 0
Baseline up to approximately 7.25 years
Primary outcome [2] 0 0
Percentage of Participants with Anti-Ocrelizumab Antibodies
Timepoint [2] 0 0
Baseline up to approximately 7.25 years
Secondary outcome [1] 0 0
Percentage of Participants with American College of Rheumatology (ACR) 20%, 50%, and 70% (ACR20/50/70) Response at Week 24
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Disease Activity Score at Week 24
Timepoint [2] 0 0
Week 24
Secondary outcome [3] 0 0
Percentage of Participants achieving European League Against Rheumatism (EULAR) Response at Week 24
Timepoint [3] 0 0
Week 24
Secondary outcome [4] 0 0
Maximum Plasma Concentration (Cmax) of Ocrelizumab
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Time to Blood B-Cell Depletion
Timepoint [5] 0 0
Baseline up to approximately 7.25 years
Secondary outcome [6] 0 0
Terminal Elimination Half-Life (t1/2) of Ocrelizumab
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity AUC(0-inf) of Ocrelizumab
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Quantifiable Concentration AUC(0-last) of Ocrelizumab
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
Time to Maximum Observed Plasma Concentration (Tmax) of Ocrelizumab
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Terminal Rate Constant of Ocrelizumab
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Systemic Clearance (CL) of Ocrelizumab
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
Mean Residence Time (MRT) of Ocrelizumab
Timepoint [12] 0 0
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)
Secondary outcome [13] 0 0
Steady State Volume of Distribution (Vss) of Ocrelizumab
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Duration of Blood B-Cell Depletion
Timepoint [14] 0 0
Baseline up to approximately 7.25 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2013
Sample size
Target
Accrual to date
Final
175
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
- Darlinghurst
Recruitment hospital [2] 0 0
- Adelaide
Recruitment hospital [3] 0 0
- Melbourne
Recruitment hospital [4] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
5041 - Adelaide
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
6979 - Perth
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Gent
Country [2] 0 0
Belgium
State/province [2] 0 0
Leuven
Country [3] 0 0
Canada
State/province [3] 0 0
Alberta
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Canada
State/province [5] 0 0
Quebec
Country [6] 0 0
Netherlands
State/province [6] 0 0
Amsterdam
Country [7] 0 0
New Zealand
State/province [7] 0 0
Auckland City
Country [8] 0 0
New Zealand
State/province [8] 0 0
Auckland
Country [9] 0 0
Russian Federation
State/province [9] 0 0
Moscow
Country [10] 0 0
Russian Federation
State/province [10] 0 0
Saint-Petersburg
Country [11] 0 0
Russian Federation
State/province [11] 0 0
St Petersburg
Country [12] 0 0
Russian Federation
State/province [12] 0 0
St. Petersburg
Country [13] 0 0
Spain
State/province [13] 0 0
Cadiz
Country [14] 0 0
Spain
State/province [14] 0 0
La Coruña
Country [15] 0 0
Spain
State/province [15] 0 0
Madrid
Country [16] 0 0
Spain
State/province [16] 0 0
Tenerife
Country [17] 0 0
Spain
State/province [17] 0 0
Barcelona
Country [18] 0 0
Spain
State/province [18] 0 0
Granada
Country [19] 0 0
Spain
State/province [19] 0 0
Sevilla
Country [20] 0 0
Spain
State/province [20] 0 0
Valencia
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Aberdeen
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Cambridge
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Derby
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Leeds
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Liverpool
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Maidstone
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Newcastle Upon Tyne
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Norwich
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Salford
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Torquay
Country [32] 0 0
United Kingdom
State/province [32] 0 0
West Midlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02720120
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02720120