Dose Finding, Efficacy and Safety of BI 655064 in Patients With Active Lupus Nephritis

Study Overview
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Brief Summary
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The overall purpose of the study is to assess the efficacy of three different doses of BI 655064 against placebo as add-on therapy to standard of care (SOC) treatment for active lupus nephritis in order to characterize the dose-response relationship within the therapeutic range, and select the target dose for phase III development.

Official Title
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A Double-blind, Randomised, Placebo-controlled Trial Evaluating the Effect of BI 655064 Administered as Sub-cutaneous Injections, on Renal Response After One Year of Treatment, in Patients With Active Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: BI 655064 dose 1
* Drug: BI 655064 dose 2
* Drug: BI 655064 dose 3
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Males and females 18-70 years. Women of childbearing potential must be ready and able (as assessed by investigator) to use simultaneously two reliable methods of birth control, one of which must be highly effective. Highly effective method, 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. Diagnosis of systemic lupus erythematosus (SLE) by American College of Rheumatology (ACR) criteria 1997, at least 4 criteria must be documented, one of which must be a positive anti-dsDNA antibody OR a positive antinuclear antibody (ANA) at screening or around time of start of induction therapy Lupus Nephritis Class III or IV (International Society of Nephrology (ISN)/Renal Pathology Society (RPS) -2003 classification) with either active or active/chronic disease, co-existing class V permitted, proven by renal biopsy within 3 months prior to screening or during screening if induction therapy has not yet been started Active renal disease evidenced by proteinuria ≥ 1.0 g/day [(Uprot/Ucrea) ≥ 1] Signed and dated written informed consent Exclusion criteria: Clinically significant current other renal disease Glomerular Filtration Rate <30ml/min/1.73m² Dialysis within 12m of screening Antiphospholipid syndrome Diabetes mellitus poorly controlled or known diabetic retinopathy or nephropathy Evidence of current or previous clinically significant disease, medical condition or finding in the medical examination that in the investigator's opinion would compromise the safety of the patient or the quality of the data Any induction therapy for Lupus Nephritis within the last 6 months prior to randomisation except induction with Mycophenolate Mofetil and high dose steroids started within 6 weeks prior to randomisation Treatment with any biologic B-cell depleting therapy (e.g. anti-CD20, anti-CD22,) within 12 months prior to randomisation Treatment with abatacept within 12 months prior to randomisation Treatment with tacrolimus or cyclosporin within 4 weeks prior to randomisation Treatment with cyclophosphamid within 6 months prior to randomisation Treatment with investigational drug within 6 months or 5 half-lives, whichever is greater before randomisation Contraindication for MMF or corticosteroids and/or known hypersensitivity to any constituents of the study drug. Chronic or relevant acute infections, including but not limited to HIV, Hepatitis B and C and tuberculosis (including a history of clinical tuberculosis (TB) and/or a positive QuantiFERON TB-Gold test Any active or suspected malignancy or history of documented malignancy within the last 5 years before screening, except appropriately treated carcinoma in situ and treated basal cell carcinoma. Live vaccination within 6 weeks before randomisation Patients unable to comply with the protocol in the investigator's opinion. Alcohol abuse in the opinion of the investigator or active drug abuse . Women who are pregnant, nursing, or who plan to become pregnant while in the trial Impaired hepatic function, defined as serum Aspartate Transferase/Alanine Transferase, bilirubin or alkaline phosphatase levels > 2 x Upper Limit of Normal Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 655064 dose 1<br> | Drug: BI 655064 dose 1<br> <br> |
| Experimental: BI 655064 dose 2<br> | Drug: BI 655064 dose 2<br> <br> |
| Experimental: BI 655064 dose 3<br> | Drug: BI 655064 dose 3<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Complete Renal Response (CRR) at Week 52 | Complete renal response (CRR) was defined as urine protein (UP) < 0.5 g/day at Week 52 and either estimated glomerular filtration rate (eGFR) within normal range at Week 52 or decrease in eGFR < 20% from baseline at Week 52 if eGFR was below normal range (below lower limit of normal [LLN], where LLN = 90 mL/min). CRR at Week 52 (derived using UP from the 24 h urine collections) was analyzed using a logistic regression model. Factors in the model included treatment and the covariates race (Asian/Non-Asian) and proteinuria at screening (UP/urine creatinine (UC) <3 or >=3 g/day). Pairwise comparisons of the modelled proportions of patients with CRR at each dose level to placebo were performed. | At week 52. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Complete Renal Response (CRR) at Week 26 | Complete renal response (CRR) was defined as urine protein (UP) < 0.5 g/day at Week 26 and either estimated glomerular filtration rate (eGFR) within normal range at Week 26 or decrease in eGFR < 20% from baseline at Week 26 if eGFR was below normal range (below lower limit of normal [LLN], where LLN = 90 mL/min). | At week 26. | 
| Percentage of Patients With Partial Renal Response (PRR) at Week 26 | Partial renal response (PRR) was defined as at least 50% reduction of proteinuria from baseline if estimated glomerular filtration rate (eGFR) was within normal range at time of assessment or decrease of eGFR <20% from baseline if eGFR was below normal range at time of assessment. | At week 26. | 
| Percentage of Patients With Partial Renal Response (PRR) at Week 52 | Partial renal response (PRR) was defined as at least 50% reduction of proteinuria from baseline if estimated glomerular filtration rate (eGFR) was within normal range at time of assessment or decrease of eGFR <20% from baseline if eGFR was below normal range at time of assessment. | At week 52. | 
| Percentage of Patients With Major Renal Response (MRR) at Week 26 | Major renal response was defined as follows depending on proteinuria at baseline: If baseline proteinuria was <3 g/day and patient had complete renal response (CRR) If baseline proteinuria was >= 3 g/day and proteinuria < 1 g/day and either estimated glomerular filtration rate (eGFR) within normal range or decrease in eGFR <20% from baseline at Week 26 if eGFR was below normal range (below lower limit of normal (LLN), where LLN = 90 mL/min) | At week 26. | 
| Percentage of Patients With Major Renal Response (MRR) at Week 52 | Major renal response was defined as follows depending on proteinuria at baseline: If baseline proteinuria was <3 g/day and patient had complete renal response (CRR) If baseline proteinuria was >= 3 g/day and proteinuria < 1 g/day and either estimated glomerular filtration rate (eGFR) within normal range or decrease in eGFR <20% from baseline at Week 52 if eGFR was below normal range (below lower limit of normal (LLN), where LLN = 90 mL/min) | At week 52. |