Lupus Nephritis

To evaluate long term efficacy and safety of different doses of BI 655064 versus placebo as add-on therapy to standard of care during maintenance treatment for lupus nephritis. To study the effect of steroid tapering and steroid withdrawal during maintenance treatment.

BI 655064

BI 655064
BI 655064
Placebo
Placebo

syringe/solution for injection

180 mg/mL
180 mg/mL

Primary endpoint:
- Proportion of patients with CRR and without any renal flares at week 52.
Secondary endpoints:
- Proportion of patients with proteinuria <0.8g/d and without any renal flares at week 52.
- Proportion of patients with CRR at week 52 and sustained steroid reduction to ≤5 mg/d from week 26 to week 52.
- Proportion of patients experiencing at least one renal flare during 52 weeks.
- Time to first renal flare over the course of 52 weeks.
- Change from baseline in SLEDAI at weeks 12, 26, 42 and 52.

Male or female patients.
- Women of childbearing potential* must be ready and able to use two reliable methods
of birth control simultaneously, one of which must be highly effective. Highly effective
birth control per ICH M3(R2) is a method that result in a low failure rate of less than 1%
per year when used consistently and correctly. The reliable methods of birth control must
be used before starting MMF/AZA and the trial drug; then continue during the trial period; and for at least 50 days after the last dose of MMF and trial medication. In case a female patient is treated with AZA the contraception shall continue for 90 days after treatment with AZA. A list of contraception methods meeting these criteria is provided in the patient information.
- Sexually active men must be ready to use condoms during treatment with MMF/AZA and for at least 90 days after cessation of MMF/AZA.
Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
For Group 1 patients only:
 Achieved either a CRR or a PRR or proteinuria ≤ 1g/d (or UP/UC ≤ 1) at the end of 1293.10.
For Group 2 patients only:
 Age 18 –70 years at screening. For patients in Japan, age 20 – 70 years at screening. Diagnosis of SLE by American College of Rheumatology (ACR) criteria 1997 with at least 4 criteria documented, one of which must either be a positive ANA or a positive
anti-dsDNA antibody at the time of starting induction therapy (historical data).
 Lupus Nephritis Class III or IV (co-existing class V permitted) based on ISN/RPS 2003 classification with either active or active/chronic disease, proven by renal biopsy before the start of induction therapy (historical data).
 Achieved either a CRR or a PRR or proteinuria ≤ 1.5g/d (or UP/UC ≤ 1.5) after at least 6
months of induction treatment (either with SOC (CYC or MMF-based) or SOC in combination with other available therapies used for induction treatment of LN e.g. tacrolimus, cyclosporin, experimental drug etc.); and within 12 months after initiating
induction therapy outside of 1293.10 trial.
 Steroid dose ≤ 15 mg/d prednisone-equivalent at baseline.

Evidence of current or previous clinically significant diseases or medical conditions other than lupus, or findings of the medical examination (including vital signs and ECG) that, in the opinion of the investigator, would compromise the safety of the patient or the quality of the data. This criterion provides an opportunity for the investigator to exclude patients based on clinical judgment, even if other eligibility criteria are satisfied.
 Significant central nervous system symptoms related to SLE based on investigators assessment.
 Clinically important acute or chronic infections including but not limited to HIV, hepatitis B or C.
 Impaired hepatic function defined as serum AST/ALT, bilirubin or alkaline phosphatase > 2 x ULN.
 Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 at screening (using CKD-EPI formula).
 Known hypersensitivity to any constituents of the trial medication; and/or contraindications to MMF or AZA or glucocorticoids.
 The use of any restricted medications (see section 4.2.3.1) or any drug considered likely to interfere with the safe conduct of the trial.
 Unable to comply with the protocol in the investigator’s opinion.
 Chronic alcohol or drug abuse or any condition that, in the investigator’s opinion, makes them an unreliable trial patient or unlikely to complete the trial.
Women who are pregnant, nursing, or who plan to become pregnant while in the trial. For Group 2 patients only:
 Clinically significant current non-SLE related renal diseases based on investigator’s judgment (e.g. post–infectious glomerulonephritis, pyelonephritis, interstitial nephritis, glomerulosclerosis).
 Dialysis within 12 months of screening.
 Live vaccination within 6 weeks prior to randomisation.
 Antiphospholipid syndrome defined as positive antiphospholipid antibodies and either history of any thrombotic event or history of miscarriage.
 Diabetes mellitus if poorly controlled or accompanied by known diabetic retinopathy or
diabetic nephropathy. It is in the investigator’s judgment if the diabetes is sufficiently
controlled for the patient to enter the trial.
 With regard to previous induction treatments, the following applies:
- Treatment with tacrolimus or cyclosporine or mizoribine within 1 month prior to
randomisation.
- Treatment with belimumab or other “BLyS antagonists” or another investigational
drug within 3 months or 5 half-lives, whichever is greater, prior to randomisation.
- Treatment with abatacept or cyclophosphamide within 3 months prior to
randomisation.
- Treatment with any biologic B-cell depleting therapy (e.g. anti-CD20) within 6
months prior to randomisation.
 Are not eligible according to the following tuberculosis (TB) screening criteria:
- Have signs or symptoms suggestive of current active or latent TB upon medical
history, physical examination and/or a chest radiograph (both posterior-anterior and
lateral views, taken within 3 months prior to the first administration of study drug and
read by a qualified radiologist).
- Have history of latent or active TB prior to screening, except for patients who have
documentation of having completed an adequate treatment regimen according to local
guidelines within the past 3 years and at least 6 months prior to the first
administration of study drug.
- Have positive QuantiFERON-TB Gold In-Tube test within 2 months prior to or
during screening, in which latent or active TB has not been ruled out, except for
patients with history of TB and documentation of having completed an adequate
treatment regimen at least 6 months prior to the first administration of study drug.
 Any documented active or suspected malignancy or history of malignancy within 5 years
prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ
carcinoma of uterine cervix.
 Previous enrolment in 1293.10 and did not complete the trial.