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

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

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.

Study Overview

• Status: Completed
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: BI 655064; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Woolloongabba, Australia, 4102
    • Princess Alexandra Hospital
• Canada
  • Quebec, Canada, G1V 4G2
    • CHU de Quebec-Universite Laval Research Centre
• Czechia
  • Prague, Czechia, 12850
    • Institute of Rheumathology Prague
  • Prague, Czechia, 12808
    • General University Hospital
• Germany
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Stuttgart, Germany, 70376
    • Robert-Bosch-Krankenhaus GmbH
• Greece
  • Athens, Greece, 124 62
    • University General Hospital Attikon
  • Heraklion, Crete, Greece, 71500
    • University General Hospital of Heraklion
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Prince of Wales Hospital
  • Hong Kong, Hong Kong, 999077
    • Queen Mary Hospital
• Japan
  • Hokkaido, Sapporo, Japan, 060-8648
    • Hokkaido University Hospital
  • Miyagi, Sendai, Japan, 980-8574
    • Tohoku University Hospital
  • Okayama, Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Tokyo, Bunkyo-ku, Japan, 113-8431
    • Juntendo University Hospital
• Korea, Republic of
  • Suwon, Korea, Republic of, 16499
    • Ajou University Hospital
• Malaysia
  • Klang, Malaysia, 41200
    • Hospital Tengku Ampuan Rahimah
• Mexico
  • Aguascalientes, Mexico, 20259
    • Centenario Hospital Miguel Hidalgo
  • Ciudad de Mexico, Mexico, 14080
    • Instituto Nacional de Cardiologia Ignacio Chavez
  • Ciudad de Mexico, Mexico, 14080
    • Instituto Nacional de Cs Médicas y Nutrición S Zubiran
• Philippines
  • Davao, Philippines, 8000
    • Southern Philippines Medical Center
  • Lipa City, Batangas, Philippines, 4217
    • Mary Mediatrix Medical Center
• Poland
  • Bialystok, Poland, 15-540
    • University Clinical Hospital in Bialystok I
  • Lodz, Poland, 90-153
    • Norbert Barlicki University Clinical Hospital No.1, Lodz
  • Radom, Poland, 26610
    • NZOZ Centrum Medyczne AESKULAP,Private Prac, Radom
• Portugal
  • Lisboa, Portugal, 1069-166
    • Hospital Curry Cabral, EPE
  • Lisboa, Portugal, 1649-028
    • Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital Santa Maria
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital
  • Bangkok, Thailand, 10170
    • Siriraj Hospital
  • Chiangmai, Thailand, 50200
    • Chiangmai University
  • Rajathevee, Thailand, 10400
    • Pramongkutklao Hospital
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
• United States
  • Florida
    • Plantation, Florida, United States, 33324
      • Integral Rheumatology and Immunology Specialist
  • New York
    • Great Neck, New York, United States, 11021
      • Northwell Health
    • Manhasset, New York, United States, 11030
      • Feinstein Institute for Medical Research
    • New York, New York, United States, 10032
      • Columbia University Medical Center-New York Presbyterian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: BI 655064; subcutaneous injection
Placebo Comparator: 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.	Drug: Placebo; subcutaneous injection
Experimental: 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.	Drug: BI 655064; subcutaneous injection
Experimental: 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.	Drug: BI 655064; subcutaneous injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2018
• Primary Completion (Actual): May 25, 2021
• Study Completion (Actual): July 27, 2021

Study Registration Dates

• First Submitted: December 21, 2017
• First Submitted That Met QC Criteria: December 21, 2017
• First Posted (Actual): December 28, 2017

Study Record Updates

• Last Update Posted (Actual): July 13, 2022
• Last Update Submitted That Met QC Criteria: June 21, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis
• Other Study ID Numbers: 1293-0013; 2017-003101-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.
• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No