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

Lupus Nephritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02770170
• Other study ID #: 1293.10
• Secondary ID: 2015-001750-15
• Status: Completed
• Phase: Phase 2
• Start date: May 16, 2016
• Est. completion date: August 18, 2020

Study information

• Verified date: June 2021
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: August 18, 2020
• Est. primary completion date: June 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• BI 655064 dose 1

• BI 655064 dose 2

• BI 655064 dose 3

• Placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  France,  Germany,  Greece,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Philippines,  Poland,  Portugal,  Serbia,  Spain,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.

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