Lupus Nephritis
Conditions
Brief summary
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
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
Interventions
DRUGBI 655064
subcutaneous injection
DRUGPlacebo
subcutaneous injection
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Complete Renal Response (CRR) and Without Any Renal Flares | At Week 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Proteinuria <0.8 Grams (g)/Day (d) and Without Any Renal Flares at Week 52 | 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. |
| 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 | At Week 52 (Sustained Steroid Reduction to ≤5 mg/d was evaluated 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. |
| Percentage of Patients Experiencing at Least One Renal Flare During 52 Weeks | At Week 52 | The percentage of patients experiencing at least one renal flare during 52 weeks is reported. |
| Time to First Renal Flare Over the Course of 52 Weeks | Up to 52 weeks. | The time to first renal flare over the course of 52 weeks is reported. |
| Percentage of Patients With Confirmed Complete Renal Response (CRR) and Without Any Renal Flares | At Week 52 | 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). |
| Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 12 | At baseline and 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). |
| Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 26 | At baseline and 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). |
| Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 42 | At baseline and 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). |
| Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 52 | At baseline and 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). |
| 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 | 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. |
Countries
Australia, Canada, Czechia, Germany, Greece, Hong Kong, Japan, Malaysia, Mexico, Philippines, Poland, Portugal, South Korea, Thailand, United Kingdom, United States
Participant flow
Recruitment details
This study was 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.
Pre-assignment details
This is an extension trial with the requirement to entry that subjects responded to treatment in 1293.10 (NCT02770170) and had the desire to continue participation in a clinical trial. Subjects were screened for eligibility prior to participation in trial 1293.10 (NCT02770170).
Participants by arm
| Arm | Count |
|---|---|
| BI 655064 120 mg 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. | 7 |
| BI 655064 180 mg 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. | 15 |
| BI 655064 240 mg 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. | 21 |
| Placebo 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. | 26 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 3 | 3 |
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Overall Study | Other than listed | 0 | 0 | 0 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | BI 655064 120 mg | BI 655064 180 mg | BI 655064 240 mg |
|---|---|---|---|---|---|
| Age, Continuous | 34.8 Years STANDARD_DEVIATION 10.9 | 35.1 Years STANDARD_DEVIATION 9.9 | 31.9 Years STANDARD_DEVIATION 6.5 | 36.5 Years STANDARD_DEVIATION 8.7 | 35.4 Years STANDARD_DEVIATION 10.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 19 Participants | 3 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 50 Participants | 4 Participants | 11 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 28 Participants | 2 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 38 Participants | 3 Participants | 9 Participants | 11 Participants |
| Sex: Female, Male Female | 24 Participants | 61 Participants | 5 Participants | 13 Participants | 19 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 2 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 15 | 1 / 21 | 0 / 26 |
| other Total, other adverse events | 6 / 7 | 11 / 15 | 15 / 21 | 15 / 26 |
| serious Total, serious adverse events | 1 / 7 | 2 / 15 | 6 / 21 | 4 / 26 |
Outcome results
Primary
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.
Time frame: At Week 52
Population: Intent to treat (ITT) set: this patient set included all patients from the treated set (TS) who had a baseline proteinuria (spot urine could be a used if the patient did not have 24 hours urine collections) and a baseline Estimated glomerular filtration rate (eGFR) value. Only subjects with non-missing results were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 655064 120 mg | Percentage of Patients With Complete Renal Response (CRR) and Without Any Renal Flares | 51.83 Percentage of participants |
| BI 655064 180 mg | Percentage of Patients With Complete Renal Response (CRR) and Without Any Renal Flares | 48.15 Percentage of participants |
| BI 655064 240 mg | Percentage of Patients With Complete Renal Response (CRR) and Without Any Renal Flares | 59.49 Percentage of participants |
| Placebo | Percentage of Patients With Complete Renal Response (CRR) and Without Any Renal Flares | 57.51 Percentage of participants |
p-value: 0.795780% CI: [-34.192, 22.825]Regression, Logistic
p-value: 0.581180% CI: [-31.178, 12.44]Regression, Logistic
p-value: 0.897280% CI: [-17.534, 21.48]Regression, Logistic
Secondary
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).
Time frame: At baseline and at Week 12
Population: Intent to treat (ITT) set: this patient set included all patients from the treated set (TS) who had a baseline proteinuria (spot urine could be a used if the patient did not have 24 hours urine collections) and a baseline Estimated glomerular filtration rate (eGFR) value. Only subjects with non-missing results were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 655064 120 mg | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 12 | -8.4 Score on a scale | Standard Deviation 5.8 |
| BI 655064 180 mg | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 12 | -7.5 Score on a scale | Standard Deviation 4.3 |
| BI 655064 240 mg | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 12 | -9.3 Score on a scale | Standard Deviation 4.9 |
| Placebo | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 12 | -7.7 Score on a scale | Standard Deviation 6.1 |
Secondary
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).
Time frame: At baseline and at Week 26
Population: Intent to treat (ITT) set: this patient set included all patients from the treated set (TS) who had a baseline proteinuria (spot urine could be a used if the patient did not have 24 hours urine collections) and a baseline Estimated glomerular filtration rate (eGFR) value. Only subjects with non-missing results were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 655064 120 mg | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 26 | -8.7 Score on a scale | Standard Deviation 5.7 |
| BI 655064 180 mg | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 26 | -7.9 Score on a scale | Standard Deviation 3.5 |
| BI 655064 240 mg | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 26 | -11.3 Score on a scale | Standard Deviation 4.8 |
| Placebo | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 26 | -5.9 Score on a scale | Standard Deviation 5.2 |
Secondary
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).
Time frame: At baseline and at Week 42
Population: Intent to treat (ITT) set: this patient set included all patients from the treated set (TS) who had a baseline proteinuria (spot urine could be a used if the patient did not have 24 hours urine collections) and a baseline Estimated glomerular filtration rate (eGFR) value. Only subjects with non-missing results were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 655064 120 mg | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 42 | -6.6 Score on a scale | Standard Deviation 3.4 |
| BI 655064 180 mg | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 42 | -6.3 Score on a scale | Standard Deviation 2.4 |
| BI 655064 240 mg | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 42 | -11.1 Score on a scale | Standard Deviation 5.1 |
| Placebo | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 42 | -6.5 Score on a scale | Standard Deviation 6.7 |
Secondary
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).
Time frame: At baseline and at Week 52
Population: Intent to treat (ITT) set: this patient set included all patients from the treated set (TS) who had a baseline proteinuria (spot urine could be a used if the patient did not have 24 hours urine collections) and a baseline Estimated glomerular filtration rate (eGFR) value. Only subjects with non-missing results were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 655064 120 mg | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 52 | -8.9 Score on a scale | Standard Deviation 6.1 |
| BI 655064 180 mg | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 52 | -7.2 Score on a scale | Standard Deviation 4 |
| BI 655064 240 mg | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 52 | -10.6 Score on a scale | Standard Deviation 4.9 |
| Placebo | Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Total Score at Week 52 | -5.3 Score on a scale | Standard Deviation 8 |
Secondary
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.
Time frame: At Week 52
Population: Intent to treat (ITT) set: this patient set included all patients from the treated set (TS) who had a baseline proteinuria (spot urine could be a used if the patient did not have 24 hours urine collections) and a baseline Estimated glomerular filtration rate (eGFR) value. Only subjects with non-missing results were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 655064 120 mg | Percentage of Patients Experiencing at Least One Renal Flare During 52 Weeks | 0 Percentage of participants |
| BI 655064 180 mg | Percentage of Patients Experiencing at Least One Renal Flare During 52 Weeks | 21.4 Percentage of participants |
| BI 655064 240 mg | Percentage of Patients Experiencing at Least One Renal Flare During 52 Weeks | 0 Percentage of participants |
| Placebo | Percentage of Patients Experiencing at Least One Renal Flare During 52 Weeks | 16.0 Percentage of participants |
p-value: 0.792180% CI: [-10.19, 23.57]Barnard test
Secondary
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.
Time frame: At Week 52 (Sustained Steroid Reduction to ≤5 mg/d was evaluated from Week 26 to Week 52).
Population: Intent to treat (ITT) set: this patient set included all patients from the treated set (TS) who had a baseline proteinuria (spot urine could be a used if the patient did not have 24 hours urine collections) and a baseline Estimated glomerular filtration rate (eGFR) value. Only subjects with non-missing results were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 655064 120 mg | 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 | 42.9 Percentage of participants |
| BI 655064 180 mg | 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 | 42.9 Percentage of participants |
| BI 655064 240 mg | 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 | 55.6 Percentage of participants |
| Placebo | 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 | 39.1 Percentage of participants |
p-value: 0.911980% CI: [-20.53, 29.6]Barnard test
p-value: 0.85180% CI: [-16.58, 24.31]Barnard test
p-value: 0.349880% CI: [-3.53, 34.73]Barnard test
Secondary
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).
Time frame: At Week 52
Population: Intent to treat (ITT) set: this patient set included all patients from the treated set (TS) who had a baseline proteinuria (spot urine could be a used if the patient did not have 24 hours urine collections) and a baseline Estimated glomerular filtration rate (eGFR) value. Only subjects with non-missing results were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 655064 120 mg | Percentage of Patients With Confirmed Complete Renal Response (CRR) and Without Any Renal Flares | 42.9 Percentage of participants |
| BI 655064 180 mg | Percentage of Patients With Confirmed Complete Renal Response (CRR) and Without Any Renal Flares | 30.8 Percentage of participants |
| BI 655064 240 mg | Percentage of Patients With Confirmed Complete Renal Response (CRR) and Without Any Renal Flares | 50.0 Percentage of participants |
| Placebo | Percentage of Patients With Confirmed Complete Renal Response (CRR) and Without Any Renal Flares | 52.0 Percentage of participants |
p-value: 0.82580% CI: [-32.83, 17.02]Barnard test
p-value: 0.256280% CI: [-39.44, 0.51]Barnard test
p-value: 0.963280% CI: [-20.45, 16.62]Barnard test
Secondary
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.
Time frame: At Week 52
Population: Intent to treat (ITT) set: this patient set included all patients from the treated set (TS) who had a baseline proteinuria (spot urine could be a used if the patient did not have 24 hours urine collections) and a baseline Estimated glomerular filtration rate (eGFR) value. Only subjects with non-missing results were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 655064 120 mg | 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 | 100.0 Percentage of participants |
| BI 655064 180 mg | 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 | 64.3 Percentage of participants |
| BI 655064 240 mg | 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 | 75.0 Percentage of participants |
| Placebo | 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 | 68.0 Percentage of participants |
p-value: 0.101680% CI: [10.28, 44.74]Barnard test
p-value: 0.832380% CI: [-23.79, 15.29]Barnard test
p-value: 0.624780% CI: [-10.5, 23.31]Barnard test
Secondary
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.
Time frame: At Week 52
Population: Intent to treat (ITT) set: this patient set included all patients from the treated set (TS) who had a baseline proteinuria (spot urine could be a used if the patient did not have 24 hours urine collections) and a baseline Estimated glomerular filtration rate (eGFR) value. Only subjects with non-missing results were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 655064 120 mg | Percentage of Patients With Proteinuria <0.8 Grams (g)/Day (d) and Without Any Renal Flares at Week 52 | 57.1 Percentage of participants |
| BI 655064 180 mg | Percentage of Patients With Proteinuria <0.8 Grams (g)/Day (d) and Without Any Renal Flares at Week 52 | 50.0 Percentage of participants |
| BI 655064 240 mg | Percentage of Patients With Proteinuria <0.8 Grams (g)/Day (d) and Without Any Renal Flares at Week 52 | 60.0 Percentage of participants |
| Placebo | Percentage of Patients With Proteinuria <0.8 Grams (g)/Day (d) and Without Any Renal Flares at Week 52 | 60.0 Percentage of participants |
p-value: 0.927580% CI: [-28.58, 21.1]Barnard test
p-value: 0.606480% CI: [-29.9, 10.64]Barnard test
80% CI: [-18.37, 18.07]
Secondary
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.
Time frame: Up to 52 weeks.
Population: Intent to treat (ITT) set: this patient set included all patients from the treated set (TS) who had a baseline proteinuria (spot urine could be a used if the patient did not have 24 hours urine collections) and a baseline Estimated glomerular filtration rate (eGFR) value. Only subject with non-missing results were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 655064 180 mg | Time to First Renal Flare Over the Course of 52 Weeks | 36.0 Weeks |
| Placebo | Time to First Renal Flare Over the Course of 52 Weeks | 37.5 Weeks |