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.
Brief Title
Dose Finding, Efficacy and Safety of BI 655064 in Patients With Active Lupus Nephritis
Categories
Completion Date
Completion Date Type
Actual
Conditions
Lupus Nephritis
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.
* 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.
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
70 Years
Minimum Age
18 Years
NCT Id
NCT02770170
Org Class
Industry
Org Full Name
Boehringer Ingelheim
Org Study Id
1293.10
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
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.
Outcome Measure
Percentage of Patients With Complete Renal Response (CRR) at Week 52
Outcome Time Frame
At week 52.
Secondary Ids
Secondary Id
2015-001750-15
Secondary Outcomes
Outcome Description
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).
Outcome Time Frame
At week 26.
Outcome Measure
Percentage of Patients With Complete Renal Response (CRR) at Week 26
Outcome Description
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.
Outcome Time Frame
At week 26.
Outcome Measure
Percentage of Patients With Partial Renal Response (PRR) at Week 26
Outcome Description
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.
Outcome Time Frame
At week 52.
Outcome Measure
Percentage of Patients With Partial Renal Response (PRR) at Week 52
Outcome Description
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)
* 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)
Outcome Time Frame
At week 26.
Outcome Measure
Percentage of Patients With Major Renal Response (MRR) at Week 26
Outcome Description
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)
* 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)
Outcome Time Frame
At week 52.
Outcome Measure
Percentage of Patients With Major Renal Response (MRR) at Week 52
See Also Links
Url
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
70
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Chaim Putterman
Investigator Email
chaim.putterman@einsteinmed.org
Investigator Phone
718-430-4266