RING – RItuximab for lupus Nephritis with remissionas a Goal, an investigator-initiated randomized international openmulticentric study

Phase 1

Conditions: upus Nephritis
MedDRA version: 18.0Level: PTClassification code 10025140Term: Lupus nephritisSystem Organ Class: 10038359 - Renal and urinary disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Lupus Nephritis

Registration Number: EUCTR2012-003314-13-DE

Lead Sponsor: Cliniques Universitaires Saint Luc, Université catholique de Louvain, Bruxelles

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 194

Inclusion Criteria

Inclusion criteria (at screening)
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) ;(minors will be included as LN is not uncommon in female teenagers. The disease can be very refractory to SOC)
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; iv): AZA for at least 6 months
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).
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 179
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
;
Inclusion criteria (at screening)
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) ;(minors will be included as LN is not uncommon in female teenagers. The disease can be very refractory to SOC)
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; iv): AZA for at least 6 months
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).
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 179
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
;
Inclusion criteria (at screening)
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) ;(minors will be included as LN is not uncommon in female teenagers. The disease can be very refractory to SOC)
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; iv): AZA for at least 6 months
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).
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 179
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion criteria (at screening, except exclusion criteria 1 at
randomization).
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 ;(excluded at screening by test)
9. Active HBV/HCV/TB infection (excluded at screening by test);
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
11. history of severe allergic or anaphylactic reaction to humanized or monoclonal antibodies or murine monoclonal antibodies, or known hypersensitivity to any component of RTX
12. active infections requiring hospitalizations or treatment with IV anti-infectives within 4 weeks prior screening
13.treatment with a life or attenuated vaccine within 28 days prior to randomization
14. grade 3 laboratoy abnormalities, dealing with haematology and liver tests, will be excluded, unless these are lupus-related
;
Exclusion criteria (at screening, except exclusion criteria 1 at
randomization).
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 ;(excluded at screening by test)
9. Active HBV/HCV/TB infection (excluded at screening by test);
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
11. history of severe allergic or anaphylactic reaction to humanized or monoclonal antibodies or murine monoclonal antibodies, or known hypersensitivity to any component of RTX
12. active infections requiring hospitalizations or treatment with IV anti-infectives within 4 weeks prior screening
13.treatment with a life or attenuated vaccine within 28 days prior to randomization
14. grade 3 laboratoy abnormalities, dealing with haematology and liver tests, will be excluded, unless these are lupus-related
;
Exclusion criteria (at screening, except exclusion criteria 1 at
randomization).
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 ;(excluded at screening by test)
9. Active HBV/HCV/TB infection (excluded at screening by test);
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
11. history of severe allergic or anaphylactic reaction to humanized or monoclonal antibodies or murine monoclonal antibodies, or known hypersensitivity to any component of RTX
12. active infections requiring hospitalizations or treatment with IV anti-infectives within 4 weeks prior screening
13.treatment with a life or attenuated vaccine within 28 days prior to randomization
14. grade 3 laboratoy abnormalities, dealing with haematology and liver tests, will be excluded, unless these are lupus-related

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method