RING - Rituximab for Lupus Nephritis With Remission as a Goal

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2012 by Université Catholique de Louvain
Sponsor:
Collaborators:
European Working Party on Systemic Lupus Erythematosus
Lupus Nephritis Trial Network
Information provided by (Responsible Party):
Frédéric A. Houssiau, MD, PhD, Université Catholique de Louvain
ClinicalTrials.gov Identifier:
NCT01673295
First received: August 22, 2012
Last updated: August 27, 2012
Last verified: August 2012
  Purpose

OBJECTIVE To test whether Rituximab (RTX) is efficacious to achieve complete renal response (CR) in Lupus Nephritis (LN) patients with persistent proteinuria (≥1g/d) despite at least 6 months of standard of care (SOC).

STUDY DESIGN Investigator-initiated randomized international open multicentric 104-week study.


Condition Intervention Phase
Lupus Nephritis
Drug: RTX infusions
Other: Standard of Care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: RING - Rituximab for Lupus Nephritis With Remission as a Goal, an Investigator-initiated Randomized International Open Multicentric Study

Resource links provided by NLM:


Further study details as provided by Université Catholique de Louvain:

Primary Outcome Measures:
  • The primary endpoint is the percentage of patients achieving renal complete response (CR) at w104. [ Time Frame: 104 weeks ] [ Designated as safety issue: Yes ]

    CR is defined as :

    • uP/C ratio ≤0.5 (expressed in mg/mg) measured in a 24-h urine collection; and
    • eGFR >=60ml/min or, if <60ml/min at screening, not fallen by >20% compared to screening; and
    • no increase of glucocorticoïds (GC) throughout the study (except for two limited courses as per protocol; vide infra); and
    • no introduction of another immunosuppressant.


Estimated Enrollment: 194
Study Start Date: November 2012
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RTX group
Subjects will receive a RTX infusion (1g) at w0, w2, w24, w26, w48, w50, w72 and w74
Drug: RTX infusions
RTX + Standard of Care
Active Comparator: Control group
Subjects will not receive RTX infusions and will be followed in standard of care
Other: Standard of Care
Standard of Care only

Detailed Description:

After screening (week -8), patients enter in a run-in period of 6 weeks during which treatment is unchanged. At week -2, if persistent proteinuria is confirmed (uP/C ratio ≥1 expressed in mg/mg), patients will be randomized in a 1/1 ratio to 1 of 2 treatment groups as follows :

RTX group Subjects will receive a RTX infusion (1g) at w0, w2, w24, w26, w48, w50,w72 and w74.Control group Subjects will not receive RTX infusions. In both arms, azathioprine (AZA) or mycophenolate mofetil (MMF) will be continued. If prescribed, prednisolone dose should not be > 10 mg/day.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All the following inclusion criteria are to be met :

  1. SLE, according to ACR and/or SLICC (Arthritis Rheum 2012; May 2; doi: 10.1002/art.34473) criteria ;
  2. Age ≥15y (except if local ethics committee imposes ≥18y) ;
  3. ISN/RPS 2003 Class III (A or A/C), IV (A or A/C ; S or G) or V lupus GN confirmed on renal biopsy performed within 24 months before screening ;
  4. Having received one out of four following immunosuppressive regimens:

    i): Euro-Lupus (EL) intravenous (IV) cyclophosphamide (CY) (6x 500 mg q2w) followed by AZA/MMF for 3 months ; ii): NIH IVCY for 6M (6 monthly pulses) followed by AZA/MMF for 3 months ; iii): MMF for at least 6 months at a dose of 2g/day (or the maximal tolerated dose; iv): AZA for at least 6 months at a dose of 2 mg/kg/day (or the maximal toerated dose).

    All patients should be on AZA or MMF at screening. In all regimens, MMF can be replaced by enteric-coated mycophenolic acid (eMPA) ;

  5. If on GC, being on maximum 10 mg equivalent prednisolone/d at screening (for at least 2 weeks) ;
  6. uP/C ratio ≥1 (expressed in mg/mg) measured in a 24-h urine collection, confirmed at randomization (w-2) ;
  7. Contraception (any type ; sexual abstinence is an alternative to contraception in paediatric patients) ;
  8. Signed informed consent (drafted according to local practice and approved by the local ethics committee).

Exclusion Criteria:

Any of the following :

  1. Recent or ongoing renal flare defined as either i) : fall in estimated glomerular filtration rate (eGFR ; MDRD) ≥25% within 3 month prior to screening or between screening and randomization ; or ii) : increase in urine protein by ≥100% to >3.5g/d compared to previous assessment ;
  2. 24-h proteinuria decline >50% over previous 6 months ;
  3. Treatment with ≥10 mg equivalent prednisolone/d in the last 2 weeks before screening ;
  4. Pregnancy or breast-feeding ;
  5. Anticipated non-compliance with the protocol ;
  6. History of malignancy (except non-melanoma skin and cervical intraepithelial cancer) ;
  7. Previous treatment with RTX (whenever) and previous treatment with another biologic agent within the last 6 months ;
  8. HIV infection ;
  9. Active HBV/HCV/TB infection ;
  10. Severe liver, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, haematologic or psychiatric disturbances, that would contraindicate inclusion in the protocol, as judged by the clinician.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01673295

Contacts
Contact: Frédéric A Houssiau, MD PHD +32 2 7645391 frederic.houssiau@uclouvain.be
Contact: Geneviève J Depresseux, Trial Coord +32 2 7645395 genevieve.depresseux@uclouvain.be

Locations
Belgium
Cliniques Universitaires Saint Luc
Bruxelles, Belgium, 1200
Sponsors and Collaborators
Frédéric A. Houssiau, MD, PhD
European Working Party on Systemic Lupus Erythematosus
Lupus Nephritis Trial Network
Investigators
Principal Investigator: Frédéric A Houssiau, MD PHD Cliniques universitaires Saint-Luc
  More Information

No publications provided

Responsible Party: Frédéric A. Houssiau, MD, PhD, Professeur Ordinaire, Chef de Service Clinique, Université Catholique de Louvain
ClinicalTrials.gov Identifier: NCT01673295     History of Changes
Other Study ID Numbers: P1200_11
Study First Received: August 22, 2012
Last Updated: August 27, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Université Catholique de Louvain:
Lupus Nephritis
Rituximab

Additional relevant MeSH terms:
Lupus Nephritis
Nephritis
Glomerulonephritis
Kidney Diseases
Urologic Diseases
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 28, 2014