An Exploratory Maintenance Trial of BI 655064 in Patients With Lupus Nephritis

Study Overview
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Brief Summary
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The main objectives of this trial are to evaluate the long term efficacy and safety of different doses of BI 655064 versus placebo as add-on therapy to Standard of Care (SOC) during maintenance therapy for lupus nephritis.

Detailed Description
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Initially planned participating countries: Argentina, Australia, Canada, Colombia, Czech Republic, France, Germany, Greece, Hong Kong, Italy, Japan, Republic of Korea, Malaysia, Mexico, Philippines, Poland, Portugal, Serbia, Spain, Taiwan, Thailand, United Kingdom, United States

Official Title
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An Exploratory Maintenance Trial Evaluating the Effect of BI 655064 in Lupus Nephritis Patients Who Have Achieved a Meaningful Response Either at the End of 1293.10 or After an Induction Treatment Outside of 1293.10

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: BI 655064
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients. Women of childbearing potential and men able to father a child 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 International Conference on Harmonisation (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 Mycophenolate mofetil/Azathioprine (MMF/AZA) and the trial drug; then continue during the trial period; and for at least 50 days after the last dose of MMF/AZA 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. Permanent sterilisation methods include hysterectomy, bilateral oophorectomy and bilateral salpingectomy. Tubal ligation is NOT a method of permanent sterilisation. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 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 Complete renal Response (CRR) or a Partial Renal Response (PRR) or proteinuria ≤ 1g/d (or UP/UC ≤ 1) at the end of 1293.10. Exclusion Criteria: 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 Systemic Lupus Erythematosus (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 Aspartate Aminotransferase/Alanine Aminotransferase (AST/ALT), bilirubin or alkaline phosphatase > 2 x Upper Limit of Normal (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 Mycophenolate mofetil (MMF) or Azathioprine (AZA) or glucocorticoids. The use of any restricted medications 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.

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 120 mg<br>120 milligrams (mg) BI 655064 were administered as solution for subcutaneous injection in a prefilled syringe once every 2 weeks plus the administration of matching placebo as subcutaneous injection in a prefilled syringe once every 2 weeks (in the alternative weeks without BI 655064 administration) over a treatment period of 52 weeks, followed by a 12-week follow-up period. The patients received 1 injection per week. | Drug: BI 655064<br>* subcutaneous injection<br>|
| Placebo Comparator: Placebo<br>Matching placebo were administered as solution for subcutaneous injection in a prefilled syringe once every week over a treatment period of 52 weeks, followed by a 12-week follow-up period. The patients received 1 injection per week. | Drug: Placebo<br>* subcutaneous injection<br>|
| Experimental: BI 655064 180 mg<br>180 milligrams (mg) BI 655064 were administered as solution for subcutaneous injection in a prefilled syringe once every 2 weeks plus the administration of matching placebo as subcutaneous injection in a prefilled syringe once every 2 weeks (in the alternative weeks without BI 655064 administration) over a treatment period of 52 weeks, followed by a 12-week follow-up period. The patients received 1 injection per week. | Drug: BI 655064<br>* subcutaneous injection<br>|
| Experimental: BI 655064 240 mg<br>120 milligrams (mg) BI 655064 were administered as solution for subcutaneous injection in a prefilled syringe once every week (240 mg every 2 weeks) over a treatment period of 52 weeks, followed by a 12-week follow-up period. The patients received 1 injection per week. | Drug: BI 655064<br>* subcutaneous injection<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) and Without Any Renal Flares | The adjusted (model-based, adjusted for race and proteinuria at screening) percentage of patients with complete renal response (CRR) and without any renal flares is reported. A logistic regression model was used including treatment and the covariates: race (Asian versus (vs.) non-Asian) and proteinuria <3 gram (g)/day vs. ≥3 g/day (or Urine protein (UP)/ Urine creatinine (UC) <3 vs. UP/UC ≥3) at screening. Complete renal response (CRR) was defined as urine protein (UP) < 0.5 g/day and either estimated glomerular filtration rate (eGFR) within normal range or decrease in eGFR < 20% from baseline if eGFR was below normal range (below lower limit of normal [LLN], where LLN = 90 mL/min. | At Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Confirmed Complete Renal Response (CRR) and Without Any Renal Flares | The percentage of patients with confirmed complete renal response (CRR) (defined as CRR at both Week 42 and Week 52 using urine protein (UP)/urine creatine (UC) ratio [UP/UC] from the spot urines) and without any renal flares is reported. Complete renal response (CRR) was defined as urine protein (UP) < 0.5 g/day and either estimated glomerular filtration rate (eGFR) within normal range or decrease in eGFR < 20% from baseline if eGFR was below normal range (below lower limit of normal [LLN], where LLN = 90 mL/min). | At Week 52 | 
| Percentage of Patients With Proteinuria <0.8 Grams (g)/Day (d) and Without Any Renal Flares at Week 52 | The percentage of patients with proteinuria <0.8 grams (g)/day (d) and without any renal flares at week 52 is reported. | At Week 52 | 
| Percentage of Patients With Complete Renal Response (CRR) at Week 52 and Sustained Steroid Reduction to ≤5 Milligrams (mg)/Day (d) From Week 26 to Week 52 | The percentage of patients with complete renal response (CRR) at Week 52 and sustained steroid reduction to ≤5 milligrams (mg)/day (d) from Week 26 to Week 52 is reported. Complete renal response (CRR) was defined as urine protein (UP) < 0.5 g/day and either estimated glomerular filtration rate (eGFR) within normal range or decrease in eGFR < 20% from baseline if eGFR was below normal range (below lower limit of normal [LLN], where LLN = 90 mL/min. | At Week 52 (Sustained Steroid Reduction to ≤5 mg/d was evaluated from Week 26 to Week 52). | 
| Percentage of Patients Experiencing at Least One Renal Flare During 52 Weeks | The percentage of patients experiencing at least one renal flare during 52 weeks is reported. | At Week 52 | 
| Time to First Renal Flare Over the Course of 52 Weeks | The time to first renal flare over the course of 52 weeks is reported. | Up to 52 weeks. | 
| Percentage of Patients With Partial Renal Response (PRR) and Without Any Renal Flares Derived From Urine Protein (UP) 24 Hours (h) Collection at Week 52 | The percentage of patients with partial renal response (PRR) and without any renal flares derived from urine protein (UP) 24 hours (h) collection at Week 52 is reported. 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 | 
| Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 12 | Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score at Week 12 is reported. Change from baseline at Week 12 is calculated as: value at Week 12 - value at baseline. SLEDAI assessment consists of 24 items capturing non-renal and renal symptoms. The total score captures non-renal and renal symptoms. Each of the 24 items has a score ranging from 1 to 8. A participant will get the score if the event of the item presents, while 0 if not. 8 items have the score 8, 6 items have the score 4, 7 items have the score 2, and 3 items have the score 1. The SLEDAI Total score is the sum of the scores of the 24 items, ranging from 0 (better health) to 105 (worse health). | At baseline and at Week 12 | 
| Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 26 | Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score at Week 26 is reported. Change from baseline at Week 26 is calculated as: value at Week 26 - value at baseline. SLEDAI assessment consists of 24 items capturing non-renal and renal symptoms. The total score captures non-renal and renal symptoms. Each of the 24 items has a score ranging from 1 to 8. A participant will get the score if the event of the item presents, while 0 if not. 8 items have the score 8, 6 items have the score 4, 7 items have the score 2, and 3 items have the score 1. The SLEDAI Total score is the sum of the scores of the 24 items, ranging from 0 (better health) to 105 (worse health). | At baseline and at Week 26 | 
| Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 42 | Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score at Week 42 is reported. Change from baseline at Week 42 is calculated as: value at Week 42 - value at baseline. SLEDAI assessment consists of 24 items capturing non-renal and renal symptoms. The total score captures non-renal and renal symptoms. Each of the 24 items has a score ranging from 1 to 8. A participant will get the score if the event of the item presents, while 0 if not. 8 items have the score 8, 6 items have the score 4, 7 items have the score 2, and 3 items have the score 1. The SLEDAI Total score is the sum of the scores of the 24 items, ranging from 0 (better health) to 105 (worse health). | At baseline and at Week 42 | 
| Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 52 | Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score at Week 52 is reported. Change from baseline at Week 52 is calculated as: value at Week 52 - value at baseline. SLEDAI assessment consists of 24 items capturing non-renal and renal symptoms. The total score captures non-renal and renal symptoms. Each of the 24 items has a score ranging from 1 to 8. A participant will get the score if the event of the item presents, while 0 if not. 8 items have the score 8, 6 items have the score 4, 7 items have the score 2, and 3 items have the score 1. The SLEDAI Total score is the sum of the scores of the 24 items, ranging from 0 (better health) to 105 (worse health). | At baseline and at Week 52 |