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NCT00476996: SCRIPT

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)

Terminated Phase 3 Results posted Last updated 12 August 2019
What this trial tests

Phase 3 trial testing Leflunomide in Rheumatoid Arthritis in 836 participants. Terminated before completion.

Timeline
15 May 2007
Primary endpoint
21 January 2010
14 May 2018

Quick facts

Lead sponsorGenentech, Inc.
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment836
Start date15 May 2007
Primary completion21 January 2010
Estimated completion14 May 2018
Sites266 locations across Italy, Panama, Japan, Taiwan, Poland, New Zealand, Netherlands, Belgium

Drugs / interventions tested

Conditions studied

Sponsor

Genentech, Inc. — full company profile →

Who can join

18 and older, any sex, with Rheumatoid Arthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses Primary · 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.

Percentage of Responders at Week 24
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD2217.1 – 26.9
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD42.236.4 – 48.1
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD47.942.0 – 53.7
Percentage of Responders at Week 48
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD19.514.8 – 24.2
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD48.742.9 – 54.6
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD50.744.9 – 56.5
Percentage of Participants With a Major Clinical Response Secondary · 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.

GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD1.80.2 – 3.4
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD4.01.7 – 6.3
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD5.73.0 – 8.4
Percentage of Participants Achieving Disease Activity Score (DAS28) Remission Secondary · 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.

Percentage of Participants at Week 24
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD1.80.2 – 3.4
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD5.83.0 – 8.5
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD6.03.3 – 8.8
Percentage of Participants at Week 48
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD1.40.0 – 2.8
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD11.98.1 – 15.7
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD12.18.3 – 15.9
Change in DAS28 From Baseline Secondary · 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.

Baseline
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD6.50± 1.014
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD6.47± 1.217
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD6.44± 1.039
Week 24
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD-0.99± 1.166
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD-1.60± 1.307
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD-1.91± 1.349
Week 48
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD-1.13± 1.404
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD-2.11± 1.348
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD-2.38± 1.496
Percentage of Participants With EULAR Response Rates of Good/ Moderate Secondary · 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.

Week 24
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD31.4
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD54.2
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD61.0
Week 48
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD24.9
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD58.8
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD60.3
Percentage of Participants Achieving an ACR50 Response Secondary · 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).

Percentage of Participants at Week 24
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD7.94.8 – 11.1
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD21.316.5 – 26.1
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD24.819.8 – 29.9
Percentage of Participants at Week 48
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD95.7 – 12.4
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD28.523.2 – 33.8
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD30.925.5 – 36.2
Percentage of Participants Achieving an ACR70 Response Secondary · 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.

Percentage of Participants at Week 24
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD2.90.9 – 4.9
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD7.64.5 – 10.7
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD9.96.4 – 13.4
Percentage of Participants at Week 48
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD4.31.9 – 6.7
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD11.27.5 – 14.9
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD18.113.6 – 22.6
Percentage of Participants With a Reduction in the HAQ-DI Score Secondary · 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.

Percentage of Participants at Week 24
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD32.927.3 – 38.4
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD52.346.5 – 58.2
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD58.552.8 – 64.3
Percentage of Participants at Week 48
GroupValue95% CI
Placebo x 2 IV + Non-Biologic DMARD23.118.1 – 28.1
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD50.544.7 – 56.4
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD51.845.9 – 57.6

Adverse events — posted to ClinicalTrials.gov

Time frame: From Day 1 to Week 48 and Week 96. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo x 2 IV + Non-Biologic DMARD
Serious: 41/276 (15%)
Deaths: 5/276
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
Serious: 46/276 (17%)
Deaths: 2/276
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
Serious: 40/284 (14%)
Deaths: 4/284
Ocrelizumab 500 mg x 2 IV + Non-biologic DMARD (OLE)
Serious: 138/664 (21%)
Deaths: 11/664

Serious adverse events (239 terms)

ReactionSystemPlacebo x 2 IV + Non-Biolo…Ocrelizumab 200 mg x 2 + N…Ocrelizumab 500 mg x 2 + N…Ocrelizumab 500 mg x 2 IV …
PneumoniaInfections and infestations————
Rheumatoid arthritisMusculoskeletal and connective tissue disorders————
Myocardial infarctionCardiac disorders————
Chest painGeneral disorders————
CellulitisInfections and infestations————
Multiple fracturesInjury, poisoning and procedural complications————
Foot deformityMusculoskeletal and connective tissue disorders————
Cerebrovascular accidentNervous system disorders————
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders————
Deep vein thrombosisVascular disorders————
AnaemiaBlood and lymphatic system disorders————
Iron deficiency anaemiaBlood and lymphatic system disorders————
Angina pectorisCardiac disorders————
Atrial fibrillationCardiac disorders————
Coronary artery diseaseCardiac disorders————
Diverticular perforationGastrointestinal disorders————
Gastrointestinal haemorrhageGastrointestinal disorders————
Inguinal herniaGastrointestinal disorders————
Large intestinal obstructionGastrointestinal disorders————
PyrexiaGeneral disorders————
CholelithiasisHepatobiliary disorders————
BronchitisInfections and infestations————
DiverticulitisInfections and infestations————
GastroenteritisInfections and infestations————
Pneumonia bacterialInfections and infestations————
Other adverse events (12 terms — click to expand)

ReactionSystemPlacebo x 2 IV + Non-Biolo…Ocrelizumab 200 mg x 2 + N…Ocrelizumab 500 mg x 2 + N…Ocrelizumab 500 mg x 2 IV …
Infusion related reactionInjury, poisoning and procedural complications————
Upper respiratory tract infectionInfections and infestations————
Urinary tract infectionInfections and infestations————
NasopharyngitisInfections and infestations————
BronchitisInfections and infestations————
SinusitisInfections and infestations————
HypertensionVascular disorders————
InsomniaPsychiatric disorders————
DarrhoeaGastrointestinal disorders————
NauseaGastrointestinal disorders————
InfluenzaInfections and infestations————
HeadacheNervous system disorders————

Most-reported serious reactions: Pneumonia, Rheumatoid arthritis, Myocardial infarction, Chest pain, Cellulitis, Multiple fractures, Foot deformity, Cerebrovascular accident.

Data from ClinicalTrials.gov NCT00476996 adverse events section.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Next-generation anti-CD20 monoclonal antibodies in autoimmune disease treatment.
    Du FH, Mills EA, Mao-Draayer Y. · · 2017 · cited 120× · PMID 29143151 · DOI 10.1007/s13317-017-0100-y
  2. Antibodies to watch in 2010.
    Reichert JM. · · 2010 · cited 68× · PMID 20065640 · DOI 10.4161/mabs.2.1.10677
  3. Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program.
    Emery P, Rigby W, Tak PP, Dörner T, et al · · 2014 · cited 61× · PMID 24498318 · DOI 10.1371/journal.pone.0087379
  4. Next generation and biosimilar monoclonal antibodies: essential considerations towards regulatory acceptance in Europe. February 3-4, 2011, Freiburg, Germany.
    Reichert JM. · · 2011 · cited 23× · PMID 21487235 · DOI 10.4161/mabs.3.3.15475

Verify or expand the search:

Other trials of Leflunomide

Trials testing the same drug.

Other recruiting trials for Rheumatoid Arthritis

Currently open trials in the same condition.

Other Genentech, Inc. trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00476996.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing