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

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

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.

Study Overview

• Status: Completed
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Placebo; Drug: BI 655064 dose 1; Drug: BI 655064 dose 2; Drug: BI 655064 dose 3

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Woolloongabba, Australia, 4102
    • Princess Alexandra Hospital
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • The Prince of Wales Hospital
• Canada
  • Quebec, Canada, G1V 4G2
    • CHU de Quebec-Universite Laval Research Centre
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
• Czechia
  • Hradec Kralove, Czechia, 50005
    • Hospital Hradec Kralove
  • Prague, Czechia, 12850
    • Institute of Rheumathology Prague
  • Prague, Czechia, 12808
    • General University Hospital Prague 2, Nephrology Clinic
• France
  • Creteil, France, 94010
    • HOP Henri Mondor
  • Paris, France, 75013
    • HOP La Pitié Salpêtrière
• Germany
  • Göttingen, Germany, 37075
    • Universitätsmedizin Göttingen, Georg-August-Universität
  • Hamburg, Germany, 22763
    • Asklepios Klinik Altona
  • Köln, Germany, 50937
    • Universitätsklinikum Köln (AöR)
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • 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
  • Athens, Greece, 115 27
    • General Hospital of Athens "Laiko"
  • Heraklion, Crete, Greece, 711 10
    • University General Hospital of Heraklion
• Hong Kong
  • HK, Hong Kong, 999077
    • Prince of Wales Hospital
  • Hong Kong, Hong Kong, 999077
    • Queen Mary Hospital
• Italy
  • Padova, Italy, 35128
    • Azienda Ospedaliera Universitaria di Padova
• Japan
  • Fukuoka, Kitakyushu, Japan, 807-8556
    • Hospital of the University of Occupational and Environmental Health
  • Hokkaido, Sapporo, Japan, 060-8648
    • Hokkaido University Hospital
  • Kanagawa, Kawasaki, Japan, 216-8511
    • St. Marianna University School of Medicine 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
  • Tokyo, Shinjuku-ku, Japan, 160-8582
    • Keio University Hospital
• Korea, Republic of
  • Suwon, Korea, Republic of, 16499
    • Ajou University Hospital
• Malaysia
  • Ipoh, Malaysia, 30990
    • Hospital Raja Permaisuri Bainun
  • Klang, Malaysia, 41200
    • Hospital Tengku Ampuan Rahimah
• Mexico
  • Aguascalientes, Mexico, 20230
    • Hospital Cardiologica Aguascalientes
  • 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
  • San Luis Potosi, Mexico, 78240
    • H. Central Dr Ignacio M. P.
• Philippines
  • Angeles City, Philippines, 2009
    • Angeles University Foundation Medical Center
  • Cebu City, Philippines, 6000
    • Chong Hua Hospital
  • Cebu City, Cebu, Philippines, 6000
    • Cebu Doctors Hospital
  • 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, 92-213
    • Cent.Clin.Hosp.Med.Univ.Lodz,Electrocard
  • Lodz, Poland, 90-153
    • Norbert Barlicki University Clinical Hospital No.1, Lodz
  • Nowa Sol, Poland, 67-100
    • Clinic Medical Center; Nowa Sol
  • Radom, Poland, 26610
    • NZOZ Centrum Medyczne AESKULAP,Private Prac, Radom
  • Zamosc, Poland, 22-400
    • John Paul II Regional Hospital, Zamosc
• Portugal
  • Coimbra, Portugal, 3000-075
    • CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
  • Lisboa, Portugal, 1649-035
    • CHULN, EPE - Hospital de Santa Maria
  • Lisboa, Portugal, 1069-166
    • Hospital Curry Cabral, EPE
  • Porto, Portugal, 4200-319
    • Centro Hospitalar Universitário São João,EPE
• Serbia
  • Belgrade, Serbia, 11000
    • Military Medical Academy
  • Belgrade, Serbia, 11000
    • Institute of Rheumatology, Belgrade
  • Nis, Serbia, 18000
    • Clinical Centre Nis
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Valencia, Spain, 46017
    • Hospital Dr. Peset
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand, 10400
    • Pramongkutklao Hospital
  • Chiangmai, Thailand, 50200
    • Chiangmai University
  • Muang, Thailand, 65000
    • Naresuan University Hospital
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • Leicester, United Kingdom, LE5 4PW
    • Leicester General Hospital
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
• United States
  • California
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
  • Florida
    • Doral, Florida, United States, 33166
      • Integrity Clinical Research, LLC
    • Kissimmee, Florida, United States, 34741
      • Hope Clinical Research
    • Plantation, Florida, United States, 33324
      • Integral Rheumatology and Immunology Specialist
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • 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
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Office of Dr. Ramesh C. Gupta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo
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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 16, 2016
• Primary Completion (ACTUAL): June 23, 2020
• Study Completion (ACTUAL): August 18, 2020

Study Registration Dates

• First Submitted: May 11, 2016
• First Submitted That Met QC Criteria: May 11, 2016
• First Posted (ESTIMATE): May 12, 2016

Study Record Updates

• Last Update Posted (ACTUAL): July 12, 2021
• Last Update Submitted That Met QC Criteria: June 18, 2021
• Last Verified: June 1, 2021

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: 1293.10; 2015-001750-15 (EUDRACT_NUMBER)