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

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02770170
• Collaborator: (none)
• Enrollment: 121
• Locations: 74
• Arms: 4
• Actual Duration (Months): 51.1
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lupus Nephritis	Drug: BI 655064 dose 1; Drug: BI 655064 dose 2; Drug: BI 655064 dose 3; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 121 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 16, 2016
• Actual Primary Completion Date: Jun 23, 2020
• Actual Study Completion Date: Aug 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BI 655064 dose 1	Drug: BI 655064 dose 1
Experimental: BI 655064 dose 2	Drug: BI 655064 dose 2
Experimental: BI 655064 dose 3	Drug: BI 655064 dose 3
Placebo Comparator: Placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With Complete Renal Response (CRR) at Week 52 [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.

Secondary Outcome Measures

1. Percentage of Patients With Complete Renal Response (CRR) at Week 26 [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).

2. Percentage of Patients With Partial Renal Response (PRR) at Week 26 [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.

3. Percentage of Patients With Partial Renal Response (PRR) at Week 52 [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.

4. Percentage of Patients With Major Renal Response (MRR) at Week 26 [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)

5. Percentage of Patients With Major Renal Response (MRR) at Week 52 [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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Academic Medical Research Institute	Los Angeles	California	United States	90022
2	Integrity Clinical Research, LLC	Doral	Florida	United States	33166
3	Hope Clinical Research	Kissimmee	Florida	United States	34741
4	Integral Rheumatology and Immunology Specialist	Plantation	Florida	United States	33324
5	Emory University	Atlanta	Georgia	United States	30322
6	Northwell Health	Great Neck	New York	United States	11021
7	Feinstein Institute for Medical Research	Manhasset	New York	United States	11030
8	Columbia University Medical Center-New York Presbyterian Hospital	New York	New York	United States	10032
9	Office of Dr. Ramesh C. Gupta	Memphis	Tennessee	United States	38119
10	The Prince of Wales Hospital	Randwick	New South Wales	Australia	2031
11	Princess Alexandra Hospital	Woolloongabba		Australia	4102
12	Toronto Western Hospital	Toronto	Ontario	Canada	M5T 2S8
13	CHU de Quebec-Universite Laval Research Centre	Quebec		Canada	G1V 4G2
14	Hospital Hradec Kralove	Hradec Kralove		Czechia	50005
15	General University Hospital Prague 2, Nephrology Clinic	Prague		Czechia	12808
16	Institute of Rheumathology Prague	Prague		Czechia	12850
17	HOP Henri Mondor	Creteil		France	94010
18	HOP La Pitié Salpêtrière	Paris		France	75013
19	Universitätsmedizin Göttingen, Georg-August-Universität	Göttingen		Germany	37075
20	Asklepios Klinik Altona	Hamburg		Germany	22763
21	Universitätsklinikum Köln (AöR)	Köln		Germany	50937
22	Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck		Germany	23538
23	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz		Germany	55131
24	Robert-Bosch-Krankenhaus GmbH	Stuttgart		Germany	70376
25	General Hospital of Athens "Laiko"	Athens		Greece	115 27
26	University General Hospital Attikon	Athens		Greece	124 62
27	University General Hospital of Heraklion	Heraklion, Crete		Greece	711 10
28	Prince of Wales Hospital	HK		Hong Kong	999077
29	Queen Mary Hospital	Hong Kong		Hong Kong	999077
30	Azienda Ospedaliera Universitaria di Padova	Padova		Italy	35128
31	Hospital of the University of Occupational and Environmental Health	Fukuoka, Kitakyushu		Japan	807-8556
32	Hokkaido University Hospital	Hokkaido, Sapporo		Japan	060-8648
33	St. Marianna University School of Medicine Hospital	Kanagawa, Kawasaki		Japan	216-8511
34	Tohoku University Hospital	Miyagi, Sendai		Japan	980-8574
35	Okayama University Hospital	Okayama, Okayama		Japan	700-8558
36	Juntendo University Hospital	Tokyo, Bunkyo-ku		Japan	113-8431
37	Keio University Hospital	Tokyo, Shinjuku-ku		Japan	160-8582
38	Ajou University Hospital	Suwon		Korea, Republic of	16499
39	Hospital Raja Permaisuri Bainun	Ipoh		Malaysia	30990
40	Hospital Tengku Ampuan Rahimah	Klang		Malaysia	41200
41	Hospital Cardiologica Aguascalientes	Aguascalientes		Mexico	20230
42	Instituto Nacional de Cardiologia Ignacio Chavez	Ciudad de Mexico		Mexico	14080
43	Instituto Nacional de Cs Médicas y Nutrición S Zubiran	Ciudad de Mexico		Mexico	14080
44	H. Central Dr Ignacio M. P.	San Luis Potosi		Mexico	78240
45	Angeles University Foundation Medical Center	Angeles City		Philippines	2009
46	Cebu Doctors Hospital	Cebu City, Cebu		Philippines	6000
47	Chong Hua Hospital	Cebu City		Philippines	6000
48	Southern Philippines Medical Center	Davao		Philippines	8000
49	Mary Mediatrix Medical Center	Lipa City, Batangas		Philippines	4217
50	University Clinical Hospital in Bialystok I	Bialystok		Poland	15-540
51	Norbert Barlicki University Clinical Hospital No.1, Lodz	Lodz		Poland	90-153
52	Cent.Clin.Hosp.Med.Univ.Lodz,Electrocard	Lodz		Poland	92-213
53	Clinic Medical Center; Nowa Sol	Nowa Sol		Poland	67-100
54	NZOZ Centrum Medyczne AESKULAP,Private Prac, Radom	Radom		Poland	26610
55	John Paul II Regional Hospital, Zamosc	Zamosc		Poland	22-400
56	CHUC - Centro Hospitalar e Universitário de Coimbra, EPE	Coimbra		Portugal	3000-075
57	Hospital Curry Cabral, EPE	Lisboa		Portugal	1069-166
58	CHULN, EPE - Hospital de Santa Maria	Lisboa		Portugal	1649-035
59	Centro Hospitalar Universitário São João,EPE	Porto		Portugal	4200-319
60	Institute of Rheumatology, Belgrade	Belgrade		Serbia	11000
61	Military Medical Academy	Belgrade		Serbia	11000
62	Clinical Centre Nis	Nis		Serbia	18000
63	Hospital Vall d'Hebron	Barcelona		Spain	08035
64	Fundación Jiménez Díaz	Madrid		Spain	28040
65	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
66	Hospital Dr. Peset	Valencia		Spain	46017
67	King Chulalongkorn Memorial Hospital	Bangkok		Thailand	10330
68	Pramongkutklao Hospital	Bangkok		Thailand	10400
69	Siriraj Hospital	Bangkok		Thailand	10700
70	Chiangmai University	Chiangmai		Thailand	50200
71	Naresuan University Hospital	Muang		Thailand	65000
72	Addenbrooke's Hospital	Cambridge		United Kingdom	CB2 0QQ
73	Leicester General Hospital	Leicester		United Kingdom	LE5 4PW
74	Guy's Hospital	London		United Kingdom	SE1 9RT

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

• Study Protocol - Sep 7, 2018
• Statistical Analysis Plan - Aug 17, 2020

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02770170
• Other Study ID Numbers: 1293.10; 2015-001750-15
• First Posted: May 12, 2016
• Last Update Posted: Jul 12, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Nephritis; Lupus Nephritis

Study Results

Participant Flow

Recruitment Details	This is a double-blind, randomised, placebo-controlled trial evaluating the effect of BI 655064 administered as subcutaneous injections, on renal response after one year of treatment, in patients with active lupus nephritis.
Pre-assignment Detail	All patients were screened for eligibility prior to participation in the trial. Patients attended a specialist site which ensured that they (the patients) strictly met all inclusion and none of the exclusion criteria. Patients were not to be allocated to a treatment group if any of the entry criteria were violated.

Arm/Group Title	120 mg BI 655064	180 mg BI 655064	240 mg BI 655064	Placebo
Arm/Group Description	Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.	Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.
Period Title: Overall Study
STARTED	21	20	40	40
COMPLETED	14	17	35	33
NOT COMPLETED	7	3	5	7

Baseline Characteristics

Arm/Group Title	120 mg BI 655064	180 mg BI 655064	240 mg BI 655064	Placebo	Total
Arm/Group Description	Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.	Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.	Total of all reporting groups
Overall Participants	21	20	40	40	121
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	35.9 (11.4)	34.5 (9.9)	34.3 (10.3)	33.9 (9.8)	34.5 (10.2)
Sex: Female, Male (Count of Participants)
Female	16 76.2%	18 90%	36 90%	38 95%	108 89.3%
Male	5 23.8%	2 10%	4 10%	2 5%	13 10.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 23.8%	4 20%	8 20%	7 17.5%	24 19.8%
Not Hispanic or Latino	16 76.2%	16 80%	32 80%	33 82.5%	97 80.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	9 42.9%	9 45%	17 42.5%	17 42.5%	52 43%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 4.8%	0 0%	2 5%	1 2.5%	4 3.3%
White	9 42.9%	11 55%	21 52.5%	22 55%	63 52.1%
More than one race	1 4.8%	0 0%	0 0%	0 0%	1 0.8%
Unknown or Not Reported	1 4.8%	0 0%	0 0%	0 0%	1 0.8%
estimated glomerular filtration rate (eGFR) at baseline (mL/min/1.73 m²) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min/1.73 m²]	85.857 (34.268)	99.850 (21.109)	91.125 (32.673)	88.775 (29.914)	90.876 (30.387)

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Complete Renal Response (CRR) at Week 52
Description	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.
Time Frame	At week 52.

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) set: This patient set included all patients from the treated set who had a baseline (or screening) proteinuria (spot urine could be used if a patient did not have 24 h urine collections) and a baseline or screening estimated glomerular filtration rate (eGFR) value.

Arm/Group Title	120 mg BI 655064	180 mg BI 655064	240 mg BI 655064	Placebo
Arm/Group Description	Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.	Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.
Measure Participants	21	20	40	40
Number [Percentage of Participants]	38.32 182.5%	44.95 224.8%	44.56 111.4%	48.33 120.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg BI 655064, 180 mg BI 655064, 240 mg BI 655064, Placebo
	Comments	Multiple comparison procedures and modelling (MCPmod) techniques for logistic regression was used.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7271
	Comments	An alpha of 0.20 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
	Method	MCPMod quadratic model fit
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	120 mg BI 655064, 180 mg BI 655064, 240 mg BI 655064, Placebo
	Comments	Multiple comparison procedures and modelling (MCPmod) techniques for logistic regression was used.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6415
	Comments	An alpha of 0.20 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
	Method	MCPMod sigmoidal Emax model fit
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	120 mg BI 655064, 180 mg BI 655064, 240 mg BI 655064, Placebo
	Comments	Multiple comparison procedures and modelling (MCPmod) techniques for logistic regression was used.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7367
	Comments	An alpha of 0.20 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
	Method	MCPMod Emax model fit
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	120 mg BI 655064, 180 mg BI 655064, 240 mg BI 655064, Placebo
	Comments	Multiple comparison procedures and modelling (MCPmod) techniques for logistic regression was used.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6624
	Comments	An alpha of 0.20 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
	Method	MCPMod exponential model fit
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	120 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4645
	Comments
	Method	Regression, Logistic
	Comments	include treatment and covariates, race (Asian or non-Asian), proteinuria at screening (<3g/day or >= 3g/day)
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-10.00
	Confidence Interval	(2-Sided) 80%; -27.292 to 7.288
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence intervals calculated using delta method

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	180 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8084
	Comments
	Method	Regression, Logistic
	Comments	include treatment and covariates, race (Asian or non-Asian), proteinuria at screening (<3g/day or >= 3g/day)
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-3.38
	Confidence Interval	(2-Sided) 80%; -21.204 to 14.451
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence intervals calculated using delta method

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	240 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7398
	Comments
	Method	Regression, Logistic
	Comments	include treatment and covariates, race (Asian or non-Asian), proteinuria at screening (<3g/day or >= 3g/day)
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-3.77
	Confidence Interval	(2-Sided) 80%; -18.364 to 10.832
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence intervals calculated using delta method

2. Secondary Outcome

Title	Percentage of Patients With Complete Renal Response (CRR) at Week 26
Description	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).
Time Frame	At week 26.

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) set: This patient set included all patients from the treated set who had a baseline (or screening) proteinuria (spot urine could be used if a patient did not have 24 h urine collections) and a baseline or screening estimated glomerular filtration rate (eGFR) value.

Arm/Group Title	120 mg BI 655064	180 mg BI 655064	240 mg BI 655064	Placebo
Arm/Group Description	Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.	Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.
Measure Participants	21	20	40	40
Number [Percentage of Participants]	28.6 136.2%	50.0 250%	35.0 87.5%	37.5 93.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5773
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-8.93
	Confidence Interval	(2-Sided) 80%; -23.66 to 7.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	180 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4013
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	12.50
	Confidence Interval	(2-Sided) 80%; -4.59 to 29.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	240 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8965
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-2.50
	Confidence Interval	(2-Sided) 80%; -15.98 to 11.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

3. Secondary Outcome

Title	Percentage of Patients With Partial Renal Response (PRR) at Week 26
Description	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 26.

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) set: This patient set included all patients from the treated set who had a baseline (or screening) proteinuria (spot urine could be used if a patient did not have 24 h urine collections) and a baseline or screening estimated glomerular filtration rate (eGFR) value.

Arm/Group Title	120 mg BI 655064	180 mg BI 655064	240 mg BI 655064	Placebo
Arm/Group Description	Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.	Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.
Measure Participants	21	20	40	40
Number [Percentage of Participants]	42.9 204.3%	75.0 375%	62.5 156.3%	62.5 156.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1476
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-19.64
	Confidence Interval	(2-Sided) 80%; -35.38 to -2.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	180 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4013
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	12.50
	Confidence Interval	(2-Sided) 80%; -4.20 to 26.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	240 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 80%; -13.63 to 13.63
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

4. Secondary Outcome

Title	Percentage of Patients With Partial Renal Response (PRR) at Week 52
Description	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.

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) set: This patient set included all patients from the treated set who had a baseline (or screening) proteinuria (spot urine could be used if a patient did not have 24 h urine collections) and a baseline or screening estimated glomerular filtration rate (eGFR) value.

Arm/Group Title	120 mg BI 655064	180 mg BI 655064	240 mg BI 655064	Placebo
Arm/Group Description	Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.	Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.
Measure Participants	21	20	40	40
Number [Percentage of Participants]	33.3 158.6%	65.0 325%	55.0 137.5%	60.0 150%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0512
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-26.67
	Confidence Interval	(2-Sided) 80%; -41.52 to -9.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	180 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7597
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	5.00
	Confidence Interval	(2-Sided) 80%; -12.10 to 20.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	240 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7505
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-5.00
	Confidence Interval	(2-Sided) 80%; -18.74 to 9.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

5. Secondary Outcome

Title	Percentage of Patients With Major Renal Response (MRR) at Week 26
Description	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)
Time Frame	At week 26.

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) set: This patient set included all patients from the treated set who had a baseline (or screening) proteinuria (spot urine could be used if a patient did not have 24 h urine collections) and a baseline or screening estimated glomerular filtration rate (eGFR) value.

Arm/Group Title	120 mg BI 655064	180 mg BI 655064	240 mg BI 655064	Placebo
Arm/Group Description	Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.	Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.
Measure Participants	21	20	40	40
Number [Percentage of Participants]	28.6 136.2%	55.0 275%	37.5 93.8%	50.0 125%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1269
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-21.43
	Confidence Interval	(2-Sided) 80%; -36.03 to -4.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	180 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7889
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	5.00
	Confidence Interval	(2-Sided) 80%; -12.24 to 21.62
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	240 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2906
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-12.50
	Confidence Interval	(2-Sided) 80%; -25.99 to 1.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

6. Secondary Outcome

Title	Percentage of Patients With Major Renal Response (MRR) at Week 52
Description	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)
Time Frame	At week 52.

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) set: This patient set included all patients from the treated set who had a baseline (or screening) proteinuria (spot urine could be used if a patient did not have 24 h urine collections) and a baseline or screening estimated glomerular filtration rate (eGFR) value.

Arm/Group Title	120 mg BI 655064	180 mg BI 655064	240 mg BI 655064	Placebo
Arm/Group Description	Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.	Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.	Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.
Measure Participants	21	20	40	40
Number [Percentage of Participants]	42.9 204.3%	55.0 275%	52.5 131.3%	52.5 131.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5687
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-9.64
	Confidence Interval	(2-Sided) 80%; -25.79 to 7.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	180 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9217
	Comments
	Method	Barnard test of association
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.50
	Confidence Interval	(2-Sided) 80%; -14.67 to 19.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	240 mg BI 655064, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 80%; -14.03 to 14.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method

Adverse Events

Time Frame	From the first does of study medication until end of the 52-week treatment + 8 weeks of follow-up, up to 60 weeks.
Adverse Event Reporting Description	Treated set (TS): This patient set included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
Arm/Group Title	120 mg BI 655064		180 mg BI 655064		240 mg BI 655064		Placebo
Arm/Group Description	Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.		Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.		Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.		Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.
All Cause Mortality
	120 mg BI 655064		180 mg BI 655064		240 mg BI 655064		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Serious Adverse Events
	120 mg BI 655064		180 mg BI 655064		240 mg BI 655064		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/21 (28.6%)		6/20 (30%)		10/40 (25%)		8/40 (20%)
Blood and lymphatic system disorders
Agranulocytosis	0/21 (0%)		0/20 (0%)		0/40 (0%)		1/40 (2.5%)
Neutropenia	1/21 (4.8%)		2/20 (10%)		1/40 (2.5%)		0/40 (0%)
Cardiac disorders
Ventricular tachycardia	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Eye disorders
Chorioretinopathy	1/21 (4.8%)		0/20 (0%)		0/40 (0%)		0/40 (0%)
Ulcerative keratitis	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Gastrointestinal disorders
Diarrhoea	1/21 (4.8%)		0/20 (0%)		0/40 (0%)		0/40 (0%)
Dyspepsia	0/21 (0%)		1/20 (5%)		0/40 (0%)		0/40 (0%)
Oesophageal food impaction	1/21 (4.8%)		0/20 (0%)		0/40 (0%)		0/40 (0%)
Hepatobiliary disorders
Cholecystitis chronic	0/21 (0%)		1/20 (5%)		0/40 (0%)		0/40 (0%)
Cholelithiasis	0/21 (0%)		1/20 (5%)		0/40 (0%)		0/40 (0%)
Liver injury	0/21 (0%)		0/20 (0%)		0/40 (0%)		1/40 (2.5%)
Infections and infestations
Cellulitis	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Conjunctivitis viral	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Enterocolitis infectious	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Escherichia bacteraemia	0/21 (0%)		0/20 (0%)		0/40 (0%)		1/40 (2.5%)
Gastroenteritis	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		1/40 (2.5%)
Gastroenteritis viral	0/21 (0%)		1/20 (5%)		0/40 (0%)		0/40 (0%)
Genital herpes simplex	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Herpes zoster	1/21 (4.8%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Meningitis cryptococcal	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Perineal abscess	0/21 (0%)		0/20 (0%)		0/40 (0%)		1/40 (2.5%)
Pneumonia	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Pneumonia bacterial	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Pulmonary tuberculosis	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Pyelonephritis	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		1/40 (2.5%)
Pyelonephritis acute	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Septic shock	0/21 (0%)		0/20 (0%)		2/40 (5%)		0/40 (0%)
Upper respiratory tract infection	0/21 (0%)		1/20 (5%)		0/40 (0%)		0/40 (0%)
Urinary tract infection	1/21 (4.8%)		0/20 (0%)		0/40 (0%)		1/40 (2.5%)
Injury, poisoning and procedural complications
Foot fracture	0/21 (0%)		0/20 (0%)		0/40 (0%)		1/40 (2.5%)
Investigations
Lymphocyte count decreased	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/21 (0%)		1/20 (5%)		0/40 (0%)		0/40 (0%)
Musculoskeletal and connective tissue disorders
Arthritis	0/21 (0%)		0/20 (0%)		0/40 (0%)		1/40 (2.5%)
Systemic lupus erythematosus	1/21 (4.8%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Psychiatric disorders
Delirium	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Renal and urinary disorders
Acute kidney injury	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Lupus nephritis	0/21 (0%)		1/20 (5%)		0/40 (0%)		0/40 (0%)
Proteinuria	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		1/40 (2.5%)
Tubulointerstitial nephritis	1/21 (4.8%)		0/20 (0%)		0/40 (0%)		0/40 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Skin and subcutaneous tissue disorders
Angioedema	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	120 mg BI 655064		180 mg BI 655064		240 mg BI 655064		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/21 (81%)		13/20 (65%)		34/40 (85%)		35/40 (87.5%)
Blood and lymphatic system disorders
Anaemia	3/21 (14.3%)		0/20 (0%)		3/40 (7.5%)		1/40 (2.5%)
Leukopenia	1/21 (4.8%)		0/20 (0%)		4/40 (10%)		1/40 (2.5%)
Lymphopenia	0/21 (0%)		0/20 (0%)		5/40 (12.5%)		1/40 (2.5%)
Neutropenia	0/21 (0%)		1/20 (5%)		6/40 (15%)		1/40 (2.5%)
Endocrine disorders
Cushingoid	1/21 (4.8%)		3/20 (15%)		2/40 (5%)		2/40 (5%)
Eye disorders
Dry eye	0/21 (0%)		0/20 (0%)		1/40 (2.5%)		3/40 (7.5%)
Vision blurred	2/21 (9.5%)		1/20 (5%)		0/40 (0%)		0/40 (0%)
Gastrointestinal disorders
Diarrhoea	5/21 (23.8%)		3/20 (15%)		9/40 (22.5%)		6/40 (15%)
Vomiting	1/21 (4.8%)		1/20 (5%)		2/40 (5%)		3/40 (7.5%)
General disorders
Asthenia	2/21 (9.5%)		0/20 (0%)		1/40 (2.5%)		1/40 (2.5%)
Fatigue	2/21 (9.5%)		1/20 (5%)		1/40 (2.5%)		1/40 (2.5%)
Injection site pain	2/21 (9.5%)		1/20 (5%)		3/40 (7.5%)		0/40 (0%)
Oedema peripheral	3/21 (14.3%)		1/20 (5%)		3/40 (7.5%)		2/40 (5%)
Pyrexia	3/21 (14.3%)		0/20 (0%)		2/40 (5%)		2/40 (5%)
Infections and infestations
Bronchitis	0/21 (0%)		0/20 (0%)		2/40 (5%)		3/40 (7.5%)
Gastroenteritis	0/21 (0%)		1/20 (5%)		3/40 (7.5%)		0/40 (0%)
Herpes zoster	0/21 (0%)		1/20 (5%)		4/40 (10%)		3/40 (7.5%)
Nasopharyngitis	2/21 (9.5%)		1/20 (5%)		4/40 (10%)		7/40 (17.5%)
Oral candidiasis	2/21 (9.5%)		1/20 (5%)		0/40 (0%)		1/40 (2.5%)
Respiratory tract infection	0/21 (0%)		0/20 (0%)		3/40 (7.5%)		3/40 (7.5%)
Rhinitis	0/21 (0%)		0/20 (0%)		3/40 (7.5%)		0/40 (0%)
Upper respiratory tract infection	5/21 (23.8%)		6/20 (30%)		7/40 (17.5%)		8/40 (20%)
Urinary tract infection	1/21 (4.8%)		2/20 (10%)		4/40 (10%)		6/40 (15%)
Investigations
Lymphocyte count decreased	0/21 (0%)		0/20 (0%)		3/40 (7.5%)		0/40 (0%)
Weight increased	2/21 (9.5%)		2/20 (10%)		5/40 (12.5%)		2/40 (5%)
Metabolism and nutrition disorders
Hypercholesterolaemia	2/21 (9.5%)		0/20 (0%)		1/40 (2.5%)		1/40 (2.5%)
Hypokalaemia	0/21 (0%)		1/20 (5%)		2/40 (5%)		5/40 (12.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/21 (14.3%)		0/20 (0%)		4/40 (10%)		6/40 (15%)
Arthritis	0/21 (0%)		1/20 (5%)		4/40 (10%)		4/40 (10%)
Muscle spasms	1/21 (4.8%)		1/20 (5%)		1/40 (2.5%)		3/40 (7.5%)
Nervous system disorders
Dizziness	1/21 (4.8%)		2/20 (10%)		1/40 (2.5%)		3/40 (7.5%)
Headache	3/21 (14.3%)		1/20 (5%)		6/40 (15%)		5/40 (12.5%)
Psychiatric disorders
Insomnia	1/21 (4.8%)		2/20 (10%)		3/40 (7.5%)		1/40 (2.5%)
Respiratory, thoracic and mediastinal disorders
Cough	1/21 (4.8%)		1/20 (5%)		5/40 (12.5%)		1/40 (2.5%)
Oropharyngeal pain	0/21 (0%)		0/20 (0%)		3/40 (7.5%)		1/40 (2.5%)
Skin and subcutaneous tissue disorders
Acne	1/21 (4.8%)		0/20 (0%)		3/40 (7.5%)		0/40 (0%)
Alopecia	0/21 (0%)		3/20 (15%)		9/40 (22.5%)		7/40 (17.5%)
Erythema	0/21 (0%)		0/20 (0%)		4/40 (10%)		3/40 (7.5%)
Rash	2/21 (9.5%)		0/20 (0%)		6/40 (15%)		2/40 (5%)
Vascular disorders
Hypertension	1/21 (4.8%)		1/20 (5%)		2/40 (5%)		3/40 (7.5%)
Hypotension	0/21 (0%)		2/20 (10%)		1/40 (2.5%)		1/40 (2.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.