Lupus Nephritis MedDRA version: 20.0 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 through 70 years at the time of screening 2. Fulfils at least 4 of the 11 criteria of the revised 1982 ACR classification criteria for SLE, at least one of which must be: a. Positive antinuclear antibody (ANA) test (1:40 or higher) or b. Elevated anti-dsDNA antibodies at screening (reported as equivocal or positive results), as per the central laboratory; or c. Anti-Smith antibody at screening elevated to above normal (ie, positive or equivocal results) as per the central laboratory 3.Class III (±class V) or class IV (±class V) LN according to the World Health Organisation (WHO) or 2003 ISN/RPS classification based on a renal biopsy obtained within 12 weeks prior to signing the ICF or during the screening period 4. Urine protein to creatinine ratio >1 mg/mg (113.17 mg/mmol), obtained on a 24-hour urine collection at both: - The start of screening and - Within 14 days prior to the expected date of randomisation. Without the results of the second (stratification) sample, subjects cannot be randomised. 5. Estimated glomerular filtration rate =35 mL/min/1.73 m2 6. Must not have active or untreated latent TB on either chest radiograph or by Quantiferon gold test 7. Women of childbearing potential must have a negative serum beta-hCG test at screening and negative urine pregnancy test prior to administration of investigational product and prior to the first dose of sponsor-provided MMF Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 145 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Receipt of any investigational product (small molecule or biologic) or commercially available biologic agent within four weeks or 5 half lives prior to signing of the ICF, whichever is greater 2. Pure Class V membranous LN on a renal biopsy obtained within 12 weeks prior to signing ICF or during the screening period 3. Known intolerance to =1.0 mg/day of MMF 4. History of dialysis within 12 months prior to signing the ICF or expected need for renal replacement therapy (dialysis or renal transplant) within a 6 month period after enrolment 5. Subjects, who at the time of signing the ICF, received any of the following immunosuppressive therapies after their qualifying biopsy (a) Oral corticosteroids >0.5 mg/kg/day for more than 8 weeks or (b) Oral or IV pulse methylprednisolone >3.0 mg (cumulative dose) or (c) IV cyclophosphamide >2 pulses of high dose (=0.5 mg/m2) or >4 doses of low dose (500 mg every 2 weeks) or (d) Average MMF >2.5 mg/day (or > 1800 mg/day of enteric-coated mycophenolate sodium) for more than 8 weeks or (e) Tacrolimus >4 mg/day for more than 8 weeks 6. Major surgery within 8 weeks before signing the ICF or major surgery planned during the study period 7. History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF 8. Confirmed positive test for hepatitis B or hepatitis C 9. Any severe herpes infection at any time prior to randomization 10.Opportunistic infection requiring hospitalisation or parenteral antimicrobial treatment within 3 years prior to randomization 11. History of cancer, apart from: a. Squamous or basal cell carcinoma of the skin that has been successfully treated b. High-grade squamous intraepithelial lesion (CIN III, CIS) treated with apparent success with curative therapy = 1 year prior to randomisation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate the effect of anifrolumab plus SOC compared to placebo plus SOC on: - Proportion of subjects achieving Complete Renal Response (CRR) at Week 52 - Proportion of subjects achieving alternative CRR (aCRR) at Week 52. The difference between the CRR and the aCRR is the addition of a criterion regarding “inactive urine sediment” ;Primary end point(s): The primary endpoint used to evaluate the effect of anifrolumab compared to placebo on LN disease activity is the relative difference in change from baseline to Week 52 in the 24-hour UPCR.;Timepoint(s) of evaluation of this end point: From baseline to Week 52 ;Main Objective: To evaluate the efficacy of anifrolumab plus standard of care (SOC) compared to placebo plus SOC in subjects with active proliferative lupus nephritis measured by the relative difference in change from baseline to Week 52 in 24-hour urine protein to creatinine ratio (UPCR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: At Week 52;Secondary end point(s): Complete renal response To evaluate the effect of anifrolumab compared to placebo on renal response in LN subjects, the proportion of subjects achieving CRR at Week 52 will be used. A subject achieves CRR if all of the following criteria are met: • Estimated glomerular filtration rate (eGFR): - =80 mL/min/1.73 m2, if baseline eGFR =90 mL/min/1.73 m2 or - >85% of baseline eGFR, if baseline eGFR 85% of baseline eGFR, if baseline eGFR <90 mL/min/1.73 m2 • 24-hour UPCR <0.5 mg/mg • Inactive urine sediment (defined as <10 RBC/hpf) | — |
Countries
Argentina, Australia, Belgium, France, Germany, Hungary, Italy, Korea, Republic of, Mexico, Peru, Poland, Russian Federation, Serbia, South Africa, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed