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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/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
Sex
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
1/02/2001
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2004
Sample size
Target
Accrual to date
Final
161
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/ct2/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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02693210