A Study to Evaluate Two Doses of Ocrelizumab in Patients With Active Systemic Lupus Erythematosus (BEGIN)

NCT00539838 | Terminated Phase 3 Results

• 2 other identifiers: ACT4071gWA20499
• Study Type: interventional
• Target: 33
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase III, randomized, double blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of ocrelizumab compared to placebo when combined with a single stable background immunosuppressive medication and a corticosteroid regimen in patients with moderately to severely active systemic lupus erythematosus, who do not have moderate to severe glomerulonephritis.

Conditions

Systemic Lupus Erythematosus

Keywords

SLE

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Major Clinical Response (MCR)

  Week 48

• Number of Participants With Partial Clinical Response (PCR)

  Week 48

• Number of Non-responders (NR)

  Week 48

Secondary Outcomes (12)

• Number of Participants Who Achieved a BILAG Score of C or Better at Week 24.

  Week 24

• Time Adjusted Mean SLEDAI-2K Score

  Week 48

• Annualized Flare Rate

  Week 48 to Week 96

• Time to First Moderate to Severe Flare

  Week 48 to Week 96

• Number of Participants Who Achieved A Major Or Partial Clinical Response At Week 48 (PCR Plus MCR Proportion), Who Did Not Experience A Flare Before Week 96

  Week 48 to Week 96

Study Arms (3)

Ocrelizumab 1000 mg

EXPERIMENTAL

Ocrelizumab was administered i.v. at a dose on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks

Drug: Prednisone; Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate); Drug: Methylprednisolone; Drug: Ocrelizumab

Ocrelizumab 400 mg

EXPERIMENTAL

Ocrelizumab was administered at a dose 400 mg i.v. on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks

Drug: Prednisone; Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate); Drug: Methylprednisolone; Drug: Ocrelizumab

Placebo

PLACEBO COMPARATOR

Placebo infusions were administered on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks

Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate); Drug: Placebo

Interventions

Prednisone DRUG

Oral repeating dose

Ocrelizumab 1000 mg; Ocrelizumab 400 mg

Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate) DRUG

Oral repeating dose

Ocrelizumab 1000 mg; Ocrelizumab 400 mg; Placebo

Methylprednisolone DRUG

Intravenous repeating dose

Ocrelizumab 1000 mg; Ocrelizumab 400 mg

Ocrelizumab DRUG

Intravenous repeating dose

Ocrelizumab 1000 mg; Ocrelizumab 400 mg

Placebo DRUG

Intravenous repeating dose

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 16 years or above at the time of screening
• Diagnosis of SLE
• Active disease at screening

You may not qualify if:

• Presence of active moderate to severe glomerulonephritis
• Currently active retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia
• Lack of peripheral venous access
• Pregnancy or breast feeding mothers
• History of severe allergic or anaphylactic reactions to humanized, chimeric or murine monoclonal antibodies or i.v. immunoglobulin
• Known severe chronic pulmonary disease
• Evidence of significant or uncontrolled concomitant diseases in any organ system not related to SLE, which, in the investigator's opinion, would impair patient participation
• Concomitant condition which has required treatment with systemic corticosteroid (excluding topical or inhaled) at any time in the 52 weeks prior to screening
• Known HIV or chronic active Hepatitis B or chronic active Hepatitis C infection
• Known active infection of any kind (but excluding fungal infection of nail beds or oral thrush which has resolved before Day 1) within 30 days prior to Day 1. In addition, any major episode of infection requiring hospitalization or treatment with intravenous anti-infectives in the 30 days prior to Day 1 or oral anti-infectives in the 14 days prior to Day 1
• History of serious recurrent or chronic infection
• History of cancer (except basal cell carcinoma of the skin that has been excised and cured)
• History of alcohol or drug abuse in the 52 weeks prior to screening
• Major surgery in the 4 weeks prior to screening excluding diagnostic surgery
• Previous treatment with CAMPATH-1H

Sponsors & Collaborators

• Genentech, Inc.: lead
• Roche Pharma AG: collaborator

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Prednisone; Azathioprine; Mycophenolic Acid; Methotrexate; Methylprednisolone; ocrelizumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Aminopterin; Pterins; Pteridines; Prednisolone; Pregnadienetriols

Limitations and Caveats

The study was terminated before any patients reached the Week 48 visit. Therefore, the safety analysis included all safety data for the 33 randomized patients that were available up to the data cutoff date (22 March 2010)

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Jorn Drappa, M.D., Ph.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2007
• First Posted: October 5, 2007
• Study Start: December 19, 2007
• Primary Completion: July 12, 2011
• Study Completion: July 12, 2011
• Last Updated: September 17, 2020
• Results First Posted: September 17, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share