A Study to Evaluate Ocrelizumab in Patients With Nephritis Due to Systemic Lupus Erythematosus (BELONG)

NCT00626197 | Terminated Phase 3 Results

• 2 other identifiers: ACT4072gWA20500
• Study Type: interventional
• Target: 381
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Lupus Nephritis; Systemic Lupus Erythematosus

Keywords

SLE; Lupus; BELONG

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Achieved Complete Renal Response (CRR)

  CRR was defined as: 1. Normal serum creatinine (and with no more than a 25 percent \[%\] increase from Baseline); 2. Improvement in urinary protein:urinary creatinine ratio to less than or equal to (≤) 0.5. PRR was defined as at least 50 percent (%) reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was greater than (\>) 3, a urine protein:urine creatinine ratio of less than (\<) 3 needed to be achieved.

  Week 48

• Percentage of Participants Who Achieved Overall Response

  Overall response rate (ORR) equals (=) CRR + PRR. CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from baseline) 2. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50 % reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio is \>3, a urine protein:urine creatinine ratio of \<3 needs to be achieved.

  Week 48

Secondary Outcomes (18)

• Percentage of Participants Who Achieved a Renal Response (Partial or Complete) by Week 36, and Sustain or Improve This Response Until Week 48

  Weeks 36, 40, 44, and 48

• Time To Complete Renal Response

  Baseline up to Week 48

• Area Under the Curve (AUC) of Calculated Glomerular Filtration Rate (cGFR) Between Baseline and Week 48

  Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48

• Percentage of Participants Who Achieved A Reduction In Systemic Lupus Erythematosis Disease Activity Index (SLEDAI) -2K Score

  Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

• Time to First Renal Flare In Those Participants Who Demonstrated at Least a Partial Renal Response

  Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

Study Arms (3)

OCR 400 mg + SOC

EXPERIMENTAL

Participants received Ocrelizumab 400 mg i.v. infusion on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.

Drug: Corticosteroids; Drug: Cyclophosphamide; Drug: Mycophenolate Mofetil; Drug: Ocrelizumab; Drug: Azathioprine

OCR 1000 mg + SOC

EXPERIMENTAL

Participants received Ocrelizumab 1000 mg i.v. infusion on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.

Drug: Corticosteroids; Drug: Cyclophosphamide; Drug: Mycophenolate Mofetil; Drug: Ocrelizumab; Drug: Azathioprine

Placebo + SOC

PLACEBO COMPARATOR

Participants received placebo i.v. infusion on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks plus SOC regimen.

Drug: Corticosteroids; Drug: Cyclophosphamide; Drug: Mycophenolate Mofetil; Drug: Placebo; Drug: Azathioprine

Interventions

Corticosteroids DRUG

Intravenous and oral repeating dose

OCR 1000 mg + SOC; OCR 400 mg + SOC; Placebo + SOC

Cyclophosphamide DRUG

Cyclophosphamide was administered at a IV dose 500 mg every 2 weeks for up to 6 doses followed by maintenance treatment with azathioprine.

OCR 1000 mg + SOC; OCR 400 mg + SOC; Placebo + SOC

Mycophenolate Mofetil DRUG

Mycophenolate Mofetil was administered orally at maximum dose of 3 g/day.

OCR 1000 mg + SOC; OCR 400 mg + SOC; Placebo + SOC

Ocrelizumab DRUG

Ocrelizumab was administed at a dose and as per schedule in arm description

OCR 1000 mg + SOC; OCR 400 mg + SOC

Placebo DRUG

Placebo was administered as per schedule in arm description

Placebo + SOC

Azathioprine DRUG

Azathioprine was administered at a dose up to 2 mg/kg/day with a maximum dose of 200 mg.

OCR 1000 mg + SOC; OCR 400 mg + SOC; Placebo + SOC

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

MeSH Terms

Conditions

Lupus Nephritis; Lupus Erythematosus, Systemic

Interventions

Adrenal Cortex Hormones; Cyclophosphamide; Mycophenolic Acid; ocrelizumab; Azathioprine

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The study was terminated early due to an imbalance in serious infections in ocrelizumab-treated participants versus placebo-treated participants. Only 139 of the 381 participants randomized completed the 48 week treatment period.

Results Point of Contact

• Title: Medical Communications
• Organization: F. Hoffmann-La Roche Ltd/Genentech Inc.

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2008
• First Posted: February 29, 2008
• Study Start: February 15, 2008
• Primary Completion: October 19, 2009
• Study Completion: October 28, 2013
• Last Updated: December 22, 2020
• Results First Posted: December 22, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share