An Investigational Study to Evaluate the Safety and Effectiveness of BMS-986165 With Background Treatment in Participants With Lupus Nephritis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of BMS-986165 compared with placebo with regard to measures of kidney function in participants with lupus nephritis (LN).

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Evaluation of the Safety and Efficacy of BMS-986165 With Background Treatment in Subjects With Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: BMS-986165
* Drug: Placebo
* Drug: Mycophenolate Mofetil


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Meets the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria for Systemic Lupus Erythematosus (SLE) Renal biopsy confirming a histologic diagnosis of active Lupus Nephritis (LN) International Scociety of Nephrology/Renal Pathology Society (ISN/RPS) Classes III, IV-S, or IV-G; or Class V Urine protein:creatinine ratio (UPCR) ≥1.5 mg/mg or UPCR ≥1 mg/mg assessed with a 24-hour urine specimen Exclusion Criteria: Pure ISN/RPS Class V membranous LN Screening estimated glomerular filtration rate ≤30 mL/min/1.73 m^2 Dialysis within 12 months before screening or plans for dialysis within 6 months after enrollment in the study End-stage renal disease Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMS-986165 Dose 1<br>Specified Dose on Specified Days | Drug: BMS-986165<br>* Specified dose on specified days<br>Drug: Mycophenolate Mofetil<br>* Specified dose on specified days<br>|
| Experimental: BMS-986165 Dose 2<br>Specified Dose on Specified Days | Drug: BMS-986165<br>* Specified dose on specified days<br>Drug: Mycophenolate Mofetil<br>* Specified dose on specified days<br>|
| Placebo Comparator: Placebo for BMS-986165<br>Specified Dose on Specified Days | Drug: Placebo<br>* Specified dose on specified days<br>Drug: Mycophenolate Mofetil<br>* Specified dose on specified days<br>|
| Experimental: Mycophenolate Mofetil (MMF)<br>Specified Dose on Specified Days | Drug: Mycophenolate Mofetil<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants Experiencing Averse Events in the Blinded Treatment Period (Part B) | An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Data collected from the week 12 visit in Part A will be used for baseline values in Part B. | From baseline up to 52 weeks after first dose in Part B | 
| The Number of Participants With Clinically Significant ECG Abnormalities in the Blinded Treatment Period (Part B) | The number of participants with clinically significant abnormalities in electrocardiograms (ECGs) parameters. The following ECG parameters will be measured: HR, PR-interval, QRS-duration, QT-interval, QTc-interval. A single 12-lead ECG will be recorded after the participant has been supine for at least 5 minutes. Data collected from the week 12 visit in Part A will be used for baseline values in Part B. | From baseline up to 52 weeks after first dose in Part B | 
| The Percent Change in Vital Sign Measurements in the Blinded Treatment Period (Part B) | The percent change from baseline in Vital sign measurements including: blood pressure, heart rate, respiratory rate, and temperature. Blood pressure and heart rate are measured after the participant has been resting quietly for at least 5 minutes. Data collected from the week 12 visit in Part A will be used for baseline values in Part B. | From baseline up to 52 weeks after first dose in Part B | 
| The Number of Participants With Abnormal Laboratory Parameters of Clinical Significance in the Blinded Treatment Period (Part B) | The number of participants with abnormal laboratory parameters (Chemistry, hematology, coagulation, immunohematology) that have been considered clinically significant. Clinically relevant laboratory results are determined by the investigator. Data collected from the week 12 visit in Part A will be used for baseline values in Part B. | From baseline up to 52 weeks after first dose in Part B | 
| Percent Change From Baseline in 24-hour Urine Protein:Creatinine Ratio (UPCR) at Week 24 in the Blinded Treatment Period (Part B) | The percent change from baseline in UPCR based on 24-hour urine collections. 24-hour urine specimens measure the levels of proteins and creatinine in urine and will be used for the UPCR at baseline (week 12) and week 24. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With Partial Renal Response (PRR) at Week 24 in the Blinded Treatment Period (Part B) | The number of participants with partial renal response (PRR) defined as ≥ 50% reduction from baseline in 24-hour Urine Protein:Creatinine Ratio (UPCR). 24-hour urine specimens measure the levels of proteins and creatinine in urine and will be used for the UPCR at baseline (week 12) and week 24. | Week 24 | 
| The Number of Participants With Partial Renal Response (PRR) at Week 52 in the Blinded Treatment Period (Part B) | The number of participants with partial renal response (PRR) defined as ≥ 50% reduction from baseline in 24-hour Urine Protein:Creatinine Ratio (UPCR). 24-hour urine specimens measure the levels of proteins and creatinine in urine and will be used for the UPCR at baseline (week 12) and week 52. | Week 52 | 
| The Number of Participants With Complete Renal Response (CRR) at Week 24 in the Blinded Treatment Period (Part B) | The number of participants with complete renal response (CRR) defined as a 24-hour Urine Protein:Creatinine Ratio (UPCR) ≤ 0.5 mg/mg and an estimated glomerular filtration rate (eGFR) (using the MDRD equation) ≥ 60 mL/min or ≤ 20% decrease from baseline. | Week 24 | 
| The Number of Participants With Complete Renal Response (CRR) at Week 52 in the Blinded Treatment Period (Part B) | The number of participants with complete renal response (CRR) defined as a 24-hour Urine Protein:Creatinine Ratio (UPCR) ≤ 0.5 mg/mg and an estimated glomerular filtration rate (eGFR) (using the MDRD equation) ≥ 60 mL/min or ≤ 20% decrease from baseline. | Week 52 | 
| The Number of Participants With Complete Renal Response (CRR) Plus Successful Corticosteroid Taper to ≤ 7.5 mg/Day at Week 24 in the Blinded Treatment Period (Part B) | The number of participants with complete renal response (CRR) defined as a 24-hour Urine Protein:Creatinine Ratio (UPCR) ≤ 0.5 mg/mg and an estimated glomerular filtration rate (eGFR) (using the MDRD equation) ≥ 60 mL/min or ≤ 20% decrease from baseline who was also able to successfully taper corticosteroid use to ≤ 7.5 mg/day. | Week 24 | 
| The Number of Participants With Complete Renal Response (CRR) Plus Successful Corticosteroid Taper to ≤ 7.5 mg/Day at Week 52 in the Blinded Treatment Period (Part B) | The number of participants with complete renal response (CRR) defined as a 24-hour Urine Protein:Creatinine Ratio (UPCR) ≤ 0.5 mg/mg and an estimated glomerular filtration rate (eGFR) (using the MDRD equation) ≥ 60 mL/min or ≤ 20% decrease from baseline who was also able to successfully taper corticosteroid use to ≤ 7.5 mg/day. | Week 52 |