RING - Rituximab for Lupus Nephritis With Remission as a Goal (RING)

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Lupus Nephritis	Drug: RTX infusions; Other: Standard of Care	Phase 3

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, w48 and w72.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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	194 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (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
Study Start Date :	November 2014
Estimated Primary Completion Date :	November 2015
Estimated Study Completion Date :	November 2016

Arms and Interventions

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Arm	Intervention/treatment
Experimental: RTX group; Subjects will receive a RTX infusion (1g) at w0, w2, w24, w48 and w72.	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

Outcome Measures

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Primary Outcome Measures :

1. The primary endpoint is the percentage of patients achieving renal complete response (CR) at w104. [ Time Frame: 104 weeks ]

   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.

Eligibility Criteria

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Ages Eligible for Study:	15 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
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

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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	Recruiting
Bruxelles, Belgium, 1200
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
Principal Investigator: Frédéric A Houssiau, MD PHD

Sponsors and Collaborators

Frédéric A. Houssiau, MD, PhD

Investigators

Principal Investigator:	Frédéric A Houssiau, MD PHD	Cliniques universitaires Saint-Luc

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
First Posted:	August 27, 2012
Last Update Posted:	May 28, 2015
Last Verified:	May 2015

Keywords provided by Frédéric A. Houssiau, MD, PhD, Université Catholique de Louvain:

Lupus Nephritis; Rituximab

Additional relevant MeSH terms:

Nephritis; Lupus Nephritis; Kidney Diseases; Urologic Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Connective Tissue Diseases	Autoimmune Diseases; Immune System Diseases; Rituximab; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents