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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00476996




Registration number
NCT00476996
Ethics application status
Date submitted
18/05/2007
Date registered
22/05/2007
Date last updated
12/08/2019

Titles & IDs
Public title
A Study of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Who Don't Have a Response to Anti-TNF-a Therapy (SCRIPT)
Scientific title
A Randomized, Double-Blind, Parallel Group, International Study to Evaluate the Safety and Efficacy of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to at Least One Anti-TNF-a Therapy
Secondary ID [1] 0 0
WA20495
Secondary ID [2] 0 0
ACT3986g
Universal Trial Number (UTN)
Trial acronym
SCRIPT
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 - Leflunomide
Treatment: Drugs - Methotrexate
Treatment: Drugs - Ocrelizumab
Treatment: Drugs - Ocrelizumab
Treatment: Drugs - Placebo

Experimental: Ocrelizumab 200 mg x 2 IV + Non-Biologic DMARD Therapy - Participants will receive 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD

Experimental: Ocrelizumab 500 mg x 2 IV + Non-Biologic DMARD Therapy - Participants will receive 2 IV infusions of 500 mg of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD

Placebo Comparator: Placebo x 2 IV + Non-Biologic DMARD Therapy - Participants will receive ocrelizumab matching placebo IV in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD


Treatment: Drugs: Leflunomide
Oral repeating dose

Treatment: Drugs: Methotrexate
Oral or parenteral repeating dose

Treatment: Drugs: Ocrelizumab
Intravenous repeating dose (200mg)

Treatment: Drugs: Ocrelizumab
Intravenous repeating dose (500mg)

Treatment: Drugs: Placebo
Intravenous repeating dose

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

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses - ACR20 response: greater than or equal to (=) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale [VAS]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.
Timepoint [1] 0 0
Weeks 24 and 48
Secondary outcome [1] 0 0
Percentage of Participants With a Major Clinical Response - Major clinical response was defined as achieving an ACR70 response and maintaining this response for a consecutive period of at least 6 months.
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Percentage of Participants Achieving Disease Activity Score (DAS28) Remission - The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
Timepoint [2] 0 0
Weeks 24 and 48
Secondary outcome [3] 0 0
Change in DAS28 From Baseline - The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.
Timepoint [3] 0 0
Weeks 24 and 48
Secondary outcome [4] 0 0
Percentage of Participants With EULAR Response Rates of Good/ Moderate - The EULAR response rate was based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none.
Timepoint [4] 0 0
Weeks 24 and 48
Secondary outcome [5] 0 0
Percentage of Participants Achieving an ACR50 Response - ACR50 response is defined as a = 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, Health Assessment Questionnaire with Disability Index (HAQ-DI), and C-Reactive Protein (CRP).
Timepoint [5] 0 0
Weeks 24 and 48
Secondary outcome [6] 0 0
Percentage of Participants Achieving an ACR70 Response - ACR70 response is defined as a = 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, HAQ-DI and CRP.
Timepoint [6] 0 0
Weeks 24 and 48
Secondary outcome [7] 0 0
Percentage of Participants With a Reduction in the HAQ-DI Score - Health Assessment Questionnaire - Disability Index (HAQ-DI): The Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA. It consists of 20 questions referring to eight component. Reduction in the HAQ-DI score of 0.25 units from baseline to weeks 24 and 48 represented a minimal clinically relevant improvement.
Timepoint [7] 0 0
Weeks 24 and 48

Eligibility
Key inclusion criteria
- Adult patients, = 18 years of age

- Rheumatoid arthritis for at least 3 months

- Inadequate response to previous or current treatment with at least one anti-TNF-alpha
agent

- Receiving either leflunomide or methotrexate for = 12 weeks, with a stable dose for
the last 4 weeks

- Swollen joint count (SJC) = 4 (66 joint count) and tender joint count (TJC) = 4 (68
joint count) at screening and baseline.

- CRP = 0.6 mg/dL using a high-sensitivity assay.

- Positive rheumatoid factor or positive anti-CCP antibody or both.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Rheumatic autoimmune disease or inflammatory joint disease, other than RA

- Any surgical procedure in past 12 weeks,or planned within 48 weeks of baseline

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 3
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
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)
QLD,WA
Recruitment hospital [1] 0 0
Sunshine Coast Rheumatology Research Unit - Maroochydore
Recruitment hospital [2] 0 0
Princess Alexandra Hospital; Rheumatology - Woolloongabba
Recruitment hospital [3] 0 0
Royal Perth Hospital; Rheumatology - Shenton Park
Recruitment postcode(s) [1] 0 0
4558 - Maroochydore
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
6008 - Shenton Park
Recruitment outside Australia
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Timaru
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Callao
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Lima
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Bydgoszcz
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Elblag
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Szczecin
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Piestany
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Slovenia
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Ljubljana
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Asturias
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Barcelona
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Cadiz
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Cantabria
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LA Coruña
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Vizcaya
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Madrid
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Salamanca
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Sweden
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Linkoeping
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Uppsala
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Switzerland
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Lausanne
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Switzerland
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Zürich
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Taiwan
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Kaohsiung

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genentech, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Roche Pharma AG
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the efficacy and safety of ocrelizumab, compared with placebo, in
patients with active rheumatoid arthritis who have an inadequate response to at least one
anti-TNF-alpha therapy. Patients will be randomized to receive placebo, 200mg of intravenous
ocrelizumab, or 500mg of i.v. ocrelizumab on days 1 and 15. A repeat course of i.v. treatment
will be administered at weeks 24 and 26. All patients will receive stable doses of either
concomitant methotrexate (7.5-25mg/week) or leflunomide (10-20mg po daily) and may receive
additional DMARDs. The treatment period is planned for 48 weeks (until primary analysis) and
then participants will enter the open label phase until the drug is commercialized. Target
sample size is 1000.
Trial website
https://clinicaltrials.gov/show/NCT00476996
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/show/NCT00476996