Clinical trial NCT00626197: A Study to Evaluate Ocrelizumab in Patients With Nephritis Due to Systemic Lupus Erythematosus (BELONG)
Official title: A Randomised, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Two Doses of Ocrelizumab in Patients With WHO or ISN Class III or IV Nephritis Due to Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lupus Nephritis
Systemic Lupus Erythematosus
Keywords: SLE
Lupus
BELONG
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Roche Pharma AG
First posted: 2008-02-29
Enrollment: 381
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase III, randomized, double-blind, placebo-controlled, multicentre, parallel-group study designed to evaluate the efficacy and safety of ocrelizumab added to SOC (corticosteroid plus one of two immunosuppressant regimens) compared with placebo added to SOC in patients with WHO or ISN Class III or IV lupus nephritis.


Eligibility criteria: Inclusion Criteria:

* Age 16 years or above at the time of the screening
* Ability and willingness to provide written informed consent and to comply with the schedule of protocol requirements
* Diagnosis of SLE
* Active lupus nephritis

Exclusion Criteria:

* Currently active retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia
* Severe renal impairment
* 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 uncontrolled concomitant diseases in any organ system not related to SLE, which, in the investigator's opinion, would preclude patient participation
* Concomitant condition which has required treatment with systemic corticosteroid (excluding topical or inhaled steroids) prior to screening
* Known HIV or chronic active Hepatitis B or chronic active Hepatitis C infection
* Known active infection of any kind prior to Day 1
* History of serious recurrent or chronic infection
* History of cancer, including solid tumors, hematological malignancies and carcinoma in situ (except basal cell carcinoma of the skin that has been excised and cured).
* History of alcohol or drug abuse prior to screening
* Major surgery prior to screening, excluding diagnostic surgery
* Previous treatment with CAMPATH-1H
* Previous treatment with a BAFF directed treatment (e.g. anti-BLyS) prior to screening
* Previous treatment with a B-cell targeted therapy other than one directed at BAFF (e.g. anti-CD20, anti-CD22)
* Treatment with any investigational agent prior to screening
* Receipt of any live vaccines prior to Day 1
* Intolerance or contraindication to oral or i.v. corticosteroids
* Positive hepatitis BsAg or hepatitis C serology. Patients who are HBsAg negative but HBcAb positive may be enrolled with a negative DNA test

Primary outcomes:
measure: Number of Participants Who Achieved Complete Renal Response (CRR)
timeFrame: Week 48
measure: Percentage of Participants Who Achieved Overall Response
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants Who Achieved a Renal Response (Partial or Complete) by Week 36, and Sustain or Improve This Response Until Week 48
timeFrame: Weeks 36, 40, 44, and 48
measure: Time To Complete Renal Response
timeFrame: Baseline up to Week 48
measure: Area Under the Curve (AUC) of Calculated Glomerular Filtration Rate (cGFR) Between Baseline and Week 48
timeFrame: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48
measure: Percentage of Participants Who Achieved A Reduction In Systemic Lupus Erythematosis Disease Activity Index (SLEDAI) -2K Score
timeFrame: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
measure: Time to First Renal Flare In Those Participants Who Demonstrated at Least a Partial Renal Response
timeFrame: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
measure: Percentage of Participants Who Achieved Clinically Meaningful Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF36) From Baseline to Week 48
timeFrame: Baseline and Weeks 1, 12, 24, 36, and 48
measure: Percentage of Participants Who Achieved Clinically Meaningful Improvement in Fatigue Using the Functional Assessment of Chronic Illness Therapy (Facit) Fatigue Questionnaire From Baseline to Week 48
timeFrame: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
measure: Percentage of Participants Who Achieved Clinically Meaningful Improvement in Pain Using the Modified Brief Pain Inventory Short Form (mBPI-SF) From Baseline to Week 48
timeFrame: Baseline and Weeks 1, 12, 24, 36, and 48
measure: Health Care Visits Over the 48-Week Treatment Period
timeFrame: Weeks 1, 24, and 48
measure: Percentage of Participants Who Achieved a CRR or PRR And Who Received A Corticosteroid Dose of <10 Milligrams Per Day (mg/Day) From Week 24 to Week 48
timeFrame: Week 48
measure: Percentage of Participants Who Achieved a CRR or PRR And Who Received a Corticosteroid Dose of <5 mg/Day by Week 48
timeFrame: Week 48
measure: Average Corticosteroid Burden Measured by AUC of the Cumulative Corticosteroid Dose Between 16 and 48 Weeks
timeFrame: Weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48
measure: Percentage of Participants Who Stopped Immunosuppressants After Week 48
timeFrame: Week 48
measure: Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit
timeFrame: Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32
measure: Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL)
timeFrame: Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32
measure: Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit
timeFrame: Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32
measure: Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit
timeFrame: Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32
measure: Percentage of Participants Achieving a Major Clinical Response or a Partial Clinical Response
timeFrame: Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Other outcomes:
Locations:
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: