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

A Randomised, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Two Doses of Ocrelizumab in Patients With Active Systemic Lupus Erythematosus

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.

Study Overview

• Status: Terminated
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Placebo; Drug: Methylprednisolone; Drug: Ocrelizumab; Drug: Prednisone; Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate)

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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
• Previous treatment with a BAFF directed treatment in the 12 months prior to screening
• Previous treatment with a B-cell targeted therapy other than one directed at BAFF
• Treatment with any investigational agent, other than those above, in the 28 days prior to screening or five half-lives of the investigational drug (whichever is longer)
• Receipt of any live vaccine in the 6 weeks prior to Day 1
• Intolerance or contraindication to oral or i.v. corticosteroids
• Treatment with a second immunosuppressive or immunomodulatory drug in the 8 weeks prior to Day 1
• Prednisone dose of ≥ 0.7 mg/kg/day (or equivalent) for > 7 of the previous 30 days prior to screening
• Treatment with cyclophosphamide or a calcineurin inhibitor in the 12 weeks prior to screening
• Positive hepatitis BsAg or hepatitis C serology. Patients who are HBsAg negative but HBcAb positive may be enrolled with a negative DNA test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ocrelizumab 1000 mg; 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: Methylprednisolone; Intravenous repeating dose; Drug: Ocrelizumab; Intravenous repeating dose; Drug: Prednisone; Oral repeating dose; Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate); Oral repeating dose
EXPERIMENTAL: Ocrelizumab 400 mg; 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: Methylprednisolone; Intravenous repeating dose; Drug: Ocrelizumab; Intravenous repeating dose; Drug: Prednisone; Oral repeating dose; Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate); Oral repeating dose
PLACEBO_COMPARATOR: Placebo; Placebo infusions were administered on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks	Drug: Placebo; Intravenous repeating dose; Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate); Oral repeating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Number of Participants Who Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 72	Week 48 to Week 72
Number of Participants Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 96	Week 48 to Week 96
Change in SF-36 Subscale And Summary Scores From Baseline At Week 48	Baseline, Week 48
Change In FACIT-Fatigue Assessment From Baseline To Week 48	Baseline, Week 48
Change From Baseline In Pain Quality And Impact Of Pain On Daily Function Measured By The Brief Pain Inventory Short Form At Week 48	Baseline, Week 48
The EQ-5D Single Index Utility Score At Week 48	Baseline, Week 48
Number of Participants With Adverse Events	Up to 2.5 years

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Collaborators: Roche Pharma AG
• Investigators: Study Director: Jorn Drappa, M.D., Ph.D., Genentech, Inc.

Publications and helpful links

Helpful Links

• Ex-U.S. Study Information (Ex-US this trial is sponsored/managed by Hoffmann-La Roche)

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 19, 2007
• Primary Completion (ACTUAL): July 12, 2011
• Study Completion (ACTUAL): July 12, 2011

Study Registration Dates

• First Submitted: October 3, 2007
• First Submitted That Met QC Criteria: October 3, 2007
• First Posted (ESTIMATE): October 5, 2007

Study Record Updates

• Last Update Posted (ACTUAL): September 17, 2020
• Last Update Submitted That Met QC Criteria: August 27, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: SLE
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Reproductive Control Agents; Antitubercular Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Antibiotics, Antitubercular; Methylprednisolone; Prednisone; Ocrelizumab; Methotrexate; Azathioprine; Mycophenolic Acid; Immunosuppressive Agents
• Other Study ID Numbers: ACT4071g; WA20499

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).