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A Study of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Who Don't Have a Response to Anti-TNF-α Therapy (SCRIPT) (SCRIPT)

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ClinicalTrials.gov Identifier: NCT00476996
Recruitment Status : Terminated (Recruitment was fully completed for this study; however, the study was terminated during conduct after the primary endpoint analysis was completed.)
First Posted : May 22, 2007
Results First Posted : August 12, 2019
Last Update Posted : August 12, 2019
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Genentech, Inc.

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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Leflunomide Drug: Methotrexate Drug: Ocrelizumab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 836 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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-α Therapy
Actual Study Start Date : May 15, 2007
Actual Primary Completion Date : January 21, 2010
Actual Study Completion Date : May 14, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Ocrelizumab

Arm Intervention/treatment
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
Drug: Leflunomide
Oral repeating dose

Drug: Methotrexate
Oral or parenteral repeating dose

Drug: Ocrelizumab
Intravenous repeating dose (200mg)

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
Drug: Leflunomide
Oral repeating dose

Drug: Methotrexate
Oral or parenteral repeating dose

Drug: Ocrelizumab
Intravenous repeating dose (500mg)

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
Drug: Leflunomide
Oral repeating dose

Drug: Methotrexate
Oral or parenteral repeating dose

Drug: Placebo
Intravenous repeating dose




Primary Outcome Measures :
  1. Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses [ Time Frame: Weeks 24 and 48 ]
    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.


Secondary Outcome Measures :
  1. Percentage of Participants With a Major Clinical Response [ Time Frame: Week 48 ]
    Major clinical response was defined as achieving an ACR70 response and maintaining this response for a consecutive period of at least 6 months.

  2. Percentage of Participants Achieving Disease Activity Score (DAS28) Remission [ Time Frame: Weeks 24 and 48 ]
    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.

  3. Change in DAS28 From Baseline [ Time Frame: Weeks 24 and 48 ]
    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.

  4. Percentage of Participants With EULAR Response Rates of Good/ Moderate [ Time Frame: Weeks 24 and 48 ]
    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.

  5. Percentage of Participants Achieving an ACR50 Response [ Time Frame: Weeks 24 and 48 ]
    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).

  6. Percentage of Participants Achieving an ACR70 Response [ Time Frame: Weeks 24 and 48 ]
    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.

  7. Percentage of Participants With a Reduction in the HAQ-DI Score [ Time Frame: Weeks 24 and 48 ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00476996


Locations
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Sponsors and Collaborators
Genentech, Inc.
Roche Pharma AG
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00476996    
Other Study ID Numbers: ACT3986g
WA20495 ( Other Identifier: Genentech )
2006-005330-20 ( EudraCT Number )
First Posted: May 22, 2007    Key Record Dates
Results First Posted: August 12, 2019
Last Update Posted: August 12, 2019
Last Verified: August 2019
Keywords provided by Genentech, Inc.:
RA
SCRIPT
anti-CD20
CD20
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Leflunomide
Ocrelizumab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors