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

Lupus Nephritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03385564
• Other study ID #: 1293-0013
• Secondary ID: 2017-003101-17
• Status: Completed
• Phase: Phase 2
• Start date: January 9, 2018
• Est. completion date: July 27, 2021

Study information

• Verified date: June 2022
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: July 27, 2021
• Est. primary completion date: May 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• BI 655064
subcutaneous injection
• Placebo
subcutaneous injection

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Woolloongabba
Canada	CHU de Quebec-Universite Laval Research Centre	Quebec
Czechia	General University Hospital	Prague
Czechia	Institute of Rheumathology Prague	Prague
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Robert-Bosch-Krankenhaus GmbH	Stuttgart
Greece	University General Hospital Attikon	Athens
Greece	University General Hospital of Heraklion	Heraklion, Crete
Hong Kong	Prince of Wales Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Japan	Hokkaido University Hospital	Hokkaido, Sapporo
Japan	Tohoku University Hospital	Miyagi, Sendai
Japan	Okayama University Hospital	Okayama, Okayama
Japan	Juntendo University Hospital	Tokyo, Bunkyo-ku
Korea, Republic of	Ajou University Hospital	Suwon
Malaysia	Hospital Tengku Ampuan Rahimah	Klang
Mexico	Centenario Hospital Miguel Hidalgo	Aguascalientes
Mexico	Instituto Nacional de Cardiologia Ignacio Chavez	Ciudad de Mexico
Mexico	Instituto Nacional de Cs Médicas y Nutrición S Zubiran	Ciudad de Mexico
Philippines	Southern Philippines Medical Center	Davao
Philippines	Mary Mediatrix Medical Center	Lipa City, Batangas
Poland	University Clinical Hospital in Bialystok I	Bialystok
Poland	Norbert Barlicki University Clinical Hospital No.1, Lodz	Lodz
Poland	NZOZ Centrum Medyczne AESKULAP,Private Prac, Radom	Radom
Portugal	Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital Santa Maria	Lisboa
Portugal	Hospital Curry Cabral, EPE	Lisboa
Thailand	King Chulalongkorn Memorial Hospital	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Chiangmai University	Chiangmai
Thailand	Pramongkutklao Hospital	Rajathevee
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Guy's Hospital	London
United States	Northwell Health	Great Neck	New York
United States	Feinstein Institute for Medical Research	Manhasset	New York
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,  Germany,  Greece,  Hong Kong,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Philippines,  Poland,  Portugal,  Thailand,  United Kingdom, 

Outcome

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

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