Clinical trial NCT02770170: Dose Finding, Efficacy and Safety of BI 655064 in Patients With Active Lupus Nephritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lupus Nephritis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2016-05-12
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Patients With Complete Renal Response (CRR) at Week 52
timeFrame: At week 52.
Secondary outcomes:
measure: Percentage of Patients With Complete Renal Response (CRR) at Week 26
timeFrame: At week 26.
measure: Percentage of Patients With Partial Renal Response (PRR) at Week 26
timeFrame: At week 26.
measure: Percentage of Patients With Partial Renal Response (PRR) at Week 52
timeFrame: At week 52.
measure: Percentage of Patients With Major Renal Response (MRR) at Week 26
timeFrame: At week 26.
measure: Percentage of Patients With Major Renal Response (MRR) at Week 52
timeFrame: At week 52.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: Doral
country: United States
facility: Integrity Clinical Research, LLC
state: Florida
city: Kissimmee
country: United States
facility: Hope Clinical Research
state: Florida
city: Plantation
country: United States
facility: Integral Rheumatology and Immunology Specialist
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: Manhasset
country: United States
facility: Feinstein Institute for Medical Research
state: New York
city: New York
country: United States
facility: Columbia University Medical Center-New York Presbyterian Hospital
state: New York
city: Memphis
country: United States
facility: Office of Dr. Ramesh C. Gupta
state: Tennessee
city: Randwick
country: Australia
facility: The Prince of Wales Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval Research Centre
city: Hradec Kralove
country: Czechia
facility: Hospital Hradec Kralove
city: Prague
country: Czechia
facility: General University Hospital Prague 2, Nephrology Clinic
city: Prague
country: Czechia
facility: Institute of Rheumathology Prague
city: Creteil
country: France
facility: HOP Henri Mondor
city: Paris
country: France
facility: HOP La Pitié Salpêtrière
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen, Georg-August-Universität
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Köln
country: Germany
facility: Universitätsklinikum Köln (AöR)
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Lübeck
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus GmbH
city: Athens
country: Greece
facility: General Hospital of Athens "Laiko"
city: Athens
country: Greece
facility: University General Hospital Attikon
city: Heraklion, Crete
country: Greece
facility: University General Hospital of Heraklion
city: HK
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Padova
country: Italy
facility: Azienda Ospedaliera Universitaria di Padova
city: Fukuoka, Kitakyushu
country: Japan
facility: Hospital of the University of Occupational and Environmental Health
city: Hokkaido, Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Kanagawa, Kawasaki
country: Japan
facility: St. Marianna University School of Medicine Hospital
city: Miyagi, Sendai
country: Japan
facility: Tohoku University Hospital
city: Okayama, Okayama
country: Japan
facility: Okayama University Hospital
city: Tokyo, Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
city: Tokyo, Shinjuku-ku
country: Japan
facility: Keio University Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
city: Klang
country: Malaysia
facility: Hospital Tengku Ampuan Rahimah
city: Aguascalientes
country: Mexico
facility: Hospital Cardiologica Aguascalientes
city: Ciudad de Mexico
country: Mexico
facility: Instituto Nacional de Cardiologia Ignacio Chavez
city: Ciudad de Mexico
country: Mexico
facility: Instituto Nacional de Cs Médicas y Nutrición S Zubiran
city: San Luis Potosi
country: Mexico
facility: H. Central Dr Ignacio M. P.
city: Angeles City
country: Philippines
facility: Angeles University Foundation Medical Center
city: Cebu City, Cebu
country: Philippines
facility: Cebu Doctors Hospital
city: Cebu City
country: Philippines
facility: Chong Hua Hospital
city: Davao
country: Philippines
facility: Southern Philippines Medical Center
city: Lipa City, Batangas
country: Philippines
facility: Mary Mediatrix Medical Center
city: Bialystok
country: Poland
facility: University Clinical Hospital in Bialystok I
city: Lodz
country: Poland
facility: Norbert Barlicki University Clinical Hospital No.1, Lodz
city: Lodz
country: Poland
facility: Cent.Clin.Hosp.Med.Univ.Lodz,Electrocard
city: Nowa Sol
country: Poland
facility: Clinic Medical Center; Nowa Sol
city: Radom
country: Poland
facility: NZOZ Centrum Medyczne AESKULAP,Private Prac, Radom
city: Zamosc
country: Poland
facility: John Paul II Regional Hospital, Zamosc
city: Coimbra
country: Portugal
facility: CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
city: Lisboa
country: Portugal
facility: Hospital Curry Cabral, EPE
city: Lisboa
country: Portugal
facility: CHULN, EPE - Hospital de Santa Maria
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário São João,EPE
city: Belgrade
country: Serbia
facility: Institute of Rheumatology, Belgrade
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Nis
country: Serbia
facility: Clinical Centre Nis
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Dr. Peset
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Pramongkutklao Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiangmai
country: Thailand
facility: Chiangmai University
city: Muang
country: Thailand
facility: Naresuan University Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: