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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02693210




Registration number
NCT02693210
Ethics application status
Date submitted
23/02/2016
Date registered
26/02/2016
Date last updated
1/11/2016

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of Mabthera Alone and in Combination With Either Cyclophosphamide or Methotrexate in Patients With Rheumatoid Arthritis
Scientific title
A Randomised, Double Dummy Controlled, Parallel Group Study of the Efficacy and Safety of MabThera (Rituximab) Alone or in Combination With Either Cyclophosphamide or Methotrexate, in Patients With Rheumatoid Arthritis
Secondary ID [1] 0 0
WA16291
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 - Cyclophosphamide
Treatment: Drugs - Methotrexate
Other interventions - Placebo Cyclophosphamide
Other interventions - Placebo Methotrexate
Other interventions - Placebo Rituximab
Treatment: Drugs - Rituximab

Active Comparator: Group A: Methotrexate - Participants will receive methotrexate at dosage >=10 milligrams per week (mg/week) orally as determined by the investigator. They also receive placebo infusion on days 1 and 15 in place of rituximab and on Days 3 and 17 in place of cyclophosphamide.

Experimental: Group B: Rituximab Monotherapy - Participants will receive 1 g intravenous infusions of rituximab on Days 1 and 15. They also receive Weekly placebo orally instead of methotrexate and placebo infusion in place of cyclophosphamide on Days 3 and 17.

Experimental: Group C: Rituximab and Cyclophosphamide - Participants will receive 1g IV infusion of rituximab on Days 1 and 15 and 750 mg infusion of Cyclophosphamide on Days 3 and 17. They also receive weekly oral placebo in place of methotrexate.

Experimental: Group D: Methotrexate and Rituximab - Participants will receive >=10 mg/week methotrexate orally along with 2 times 1 gram (g) rituximab IV infusions on Days 1 and 15. Participants will also receive placebo infusions on Days 3 and 17 in place of cyclophosphamide.


Treatment: Drugs: Cyclophosphamide
Participants will receive 750 mg infusions of cyclophosphamide on Days 3 and 17

Treatment: Drugs: Methotrexate
Participants will receive >= 10 mg/week methotrexate orally up to 24 weeks

Other interventions: Placebo Cyclophosphamide
Participants will receive placebo in place of cyclophosphamide on Days 3 and 17

Other interventions: Placebo Methotrexate
Participants will receive weekly oral placebo in place of Methotrexate

Other interventions: Placebo Rituximab
Participants will receive placebo in place of rituximab on days 1 and 15

Treatment: Drugs: Rituximab
Participants will receive 1g infusions of rituximab on Days 1 and 15

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of participants achieving American College of Rheumatology (ACR) 50 response at Week 24
Timepoint [1] 0 0
Week 24
Secondary outcome [1] 0 0
Percentage of participants achieving ACR 20 and ACR 70 responses at Week 24
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Area Under the Curve (AUC) of American College of Rheumatology Response (ACRn)
Timepoint [2] 0 0
Baseline up to Week 24
Secondary outcome [3] 0 0
AUC of the mean Disease Activity Scores (DAS)
Timepoint [3] 0 0
Baseline up to Week 24
Secondary outcome [4] 0 0
Change from Baseline in the Swollen Joint Count
Timepoint [4] 0 0
Baseline, Weeks 12, 16, 20 and 24
Secondary outcome [5] 0 0
Change from Baseline in the Tender Joint Count
Timepoint [5] 0 0
Baseline, Weeks 12, 16, 20 and 24
Secondary outcome [6] 0 0
Change from Baseline in participant's global assessment of disease activity using a Visual Analog Scale (VAS)
Timepoint [6] 0 0
Baseline, Weeks 8, 12, 16, 20 and 24
Secondary outcome [7] 0 0
Change from Baseline in physician's global assessment of disease activity using VAS
Timepoint [7] 0 0
Baseline, Weeks 8, 12, 16, 20 and 24
Secondary outcome [8] 0 0
Change from Baseline in the Health Assessment Questionnaire - Disease Index (HAQ-DI) scores
Timepoint [8] 0 0
Baseline, Weeks 12, 16, 20 and 24
Secondary outcome [9] 0 0
Change from Baseline in participant's pain measured by VAS
Timepoint [9] 0 0
Baseline, Weeks 12, 16, 20 and 24
Secondary outcome [10] 0 0
Change from Baseline in C-Reactive Protein (CRP) Levels
Timepoint [10] 0 0
Baseline, Weeks 12, 16, 20 and 24
Secondary outcome [11] 0 0
Change from Baseline in Erythrocyte Sedimentation Rate (ESR)
Timepoint [11] 0 0
Baseline, Weeks 12, 16, 20 and 24
Secondary outcome [12] 0 0
Mean change in Rheumatoid factor levels at 24 weeks
Timepoint [12] 0 0
Baseline and Week 24
Secondary outcome [13] 0 0
Percentage of participants who withdrew due to insufficient therapeutic response
Timepoint [13] 0 0
Up to 24 Weeks

Eligibility
Key inclusion criteria
- Participants with moderate to severe rheumatoid arthritis (RA) who have previously
failed 1-5 DMARDS who currently have partial clinical response to treatment with
methotrexate

- Using methotrexate as a single DMARD for at least 16 weeks, of which the last 4 weeks
prior to baseline on a stable oral dose greater than or equal to (>=) 10 milligrams
per week (mg/week)

- >=21 years of age

- Swollen Joint Count (SJC) and Tender Joint Count (TJC) >= 8 (out of 66 and 68 joints
respectively)

- At least 2 of the following parameters at Baseline: C- Reactive Protein >= 15 mg/dL;
Erythrocyte Sedimentation Rate >= 30 millimeters per hour (mm/hr); Morning stiffness
>45 minutes

- Rheumatoid factor titer >=20 International units per milliliter (IU/mL)

- Corticosteroid (less than or equal to [=<] 12.5 milligrams per deciliter [mg/d]
prednisone or equivalent) or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are
permitted if stable for at least 4 weeks prior to baseline
Minimum age
21 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- American Rheumatism Association (ARA) Class IV RA disease

- Concurrent treatment with any DMARD (apart from randomized treatment) or
anti-TNF-alpha therapy

- Active infection or history of recurrent significant infection

- Prior history of cancer including solid tumors and hematologic malignancies (except
basal carcinoma of the skin that have been excised and cured)

- Evidence of serious uncontrolled concomitant diseases such as cardiovascular disease,
nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders

- Bone/joint surgery within 6 weeks prior to screening

- Rheumatic Autoimmune disease other than RA

- Active rheumatoid vasculitis

- Prior history of gout

- Chronic fatigue syndrome

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

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Darlinghurst
Recruitment hospital [2] 0 0
- Kogarah
Recruitment hospital [3] 0 0
- Woodville
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Diepenbeek
Country [2] 0 0
Belgium
State/province [2] 0 0
Gent
Country [3] 0 0
Belgium
State/province [3] 0 0
Liege
Country [4] 0 0
Canada
State/province [4] 0 0
Manitoba
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
Czech Republic
State/province [7] 0 0
Praha
Country [8] 0 0
Germany
State/province [8] 0 0
Leipzig
Country [9] 0 0
Germany
State/province [9] 0 0
Ratingen
Country [10] 0 0
Germany
State/province [10] 0 0
Wiesbaden
Country [11] 0 0
Israel
State/province [11] 0 0
Haifa
Country [12] 0 0
Italy
State/province [12] 0 0
Brescia
Country [13] 0 0
Italy
State/province [13] 0 0
Genova
Country [14] 0 0
Italy
State/province [14] 0 0
Modena
Country [15] 0 0
Italy
State/province [15] 0 0
Siena
Country [16] 0 0
Netherlands
State/province [16] 0 0
Leiden
Country [17] 0 0
Poland
State/province [17] 0 0
Lublin
Country [18] 0 0
Poland
State/province [18] 0 0
Poznan
Country [19] 0 0
Poland
State/province [19] 0 0
Warszawa
Country [20] 0 0
Poland
State/province [20] 0 0
Wroclaw
Country [21] 0 0
Spain
State/province [21] 0 0
Guadalajara
Country [22] 0 0
Spain
State/province [22] 0 0
La Laguna
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid
Country [24] 0 0
Spain
State/province [24] 0 0
Sevilla
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Cannock
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Leeds
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Stoke-on-trent

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

Ethics approval
Ethics application status

Summary
Brief summary
WA16291 is a Phase IIa "proof-of-concept" study. The primary objective of this study is to
determine the safety and efficacy of rituximab (a B cell depleting chimeric monoclonal
antibody) used either as monotherapy or in combination with methotrexate or cyclophosphamide
in participants with rheumatoid arthritis who have failed prior Disease Modifying
Anti-Rheumatic Drug (DMARD) therapy and currently have an inadequate clinical response to
methotrexate.
Trial website
https://clinicaltrials.gov/show/NCT02693210
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hofffmann-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
Other publications