Lupus Nephritis
Conditions
Brief summary
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).
Interventions
DRUGBMS-986165
Specified dose on specified days
DRUGPlacebo
Specified dose on specified days
DRUGMycophenolate Mofetil
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind Study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Experiencing Averse Events in the Blinded Treatment Period (Part B) | From baseline up to 52 weeks after first dose in 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. |
| The Number of Participants With Clinically Significant ECG Abnormalities in the Blinded Treatment Period (Part B) | From baseline up to 52 weeks after first dose in 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. |
| The Percent Change in Vital Sign Measurements in the Blinded Treatment Period (Part B) | From baseline up to 52 weeks after first dose in 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. |
| The Number of Participants With Abnormal Laboratory Parameters of Clinical Significance in the Blinded Treatment Period (Part B) | From baseline up to 52 weeks after first dose in 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. |
| Percent Change From Baseline in 24-hour Urine Protein:Creatinine Ratio (UPCR) at Week 24 in the Blinded Treatment Period (Part B) | Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Partial Renal Response (PRR) at Week 24 in the Blinded Treatment Period (Part B) | Week 24 | 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. |
| 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) | Week 52 | 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. |
| The Number of Participants With Partial Renal Response (PRR) at Week 52 in the Blinded Treatment Period (Part B) | Week 52 | 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. |
| The Number of Participants With Complete Renal Response (CRR) at Week 24 in the Blinded Treatment Period (Part B) | Week 24 | 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. |
| The Number of Participants With Complete Renal Response (CRR) at Week 52 in the Blinded Treatment Period (Part B) | Week 52 | 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. |
| 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) | Week 24 | 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. |
Countries
Australia, Belgium, Canada, China, Czechia, Germany, Israel, Italy, Mexico, Netherlands, Russia, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
Participants with an inadequate renal response to MMF may be randomized to blinded study treatment BMS-986165 3 mg BID, BMS-986165 6 mg BID, or placebo BID, as add-on therapy to MMF in Part B. No participants were randomized to receive BMS-986165 3 mg BID or placebo BID due to low enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Open Label MMF All study participants receive Mycophenolate Mofetil (MMF) at a dose of 1.5 to 3.0 g/day for 12 weeks.
Participants who meet the criteria to continue in Part B but do not meet the randomization criteria may continue on open-label MMF with or without corticosteroids.
The following suggested target doses of MMF should be reached by the time of randomization:
* 1.5 to 2.0 g/day for participants self-described as Asian or of Asian descent
* 3.0 g/day for participants self-described as Black, African American, or of African descent
* 2.0 g/day for all others | 15 |
| Open Label MMF + BMS-986165 After 12 weeks of treatment with Mycophenolate Mofetil (MMF) at a dose of 1.5 to 3.0 g/day in Part A, participants meeting randomization criteria for Part B receive BMS-986165 6 mg BID + continued open-label MMF with or without corticosteroids through 52 weeks. Randomized participants may continue to receive blinded study treatment for 52 additional weeks. | 1 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Blinded Treatment (Part B) | Study terminated by sponsor | 3 | 0 |
| Open-Label MMF Run-in (Part A) | Adverse Event | 1 | 0 |
| Open-Label MMF Run-in (Part A) | Non-compliance with study drug | 1 | 0 |
| Open-Label MMF Run-in (Part A) | Other reasons | 4 | 0 |
| Open-Label MMF Run-in (Part A) | Protocol-specified withdrawal criterion met | 1 | 0 |
| Open-Label MMF Run-in (Part A) | Study terminated by sponsor | 3 | 0 |
Baseline characteristics
| Characteristic | Open Label MMF | Open Label MMF + BMS-986165 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 1 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 0 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 5 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Female | 10 Participants | 0 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 1 |
| other Total, other adverse events | 7 / 16 | 1 / 1 |
| serious Total, serious adverse events | 1 / 16 | 1 / 1 |
Outcome results
Primary
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.
Time frame: Week 24
Population: All randomized participants in Part B
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label MMF + BMS-986165 | Percent Change From Baseline in 24-hour Urine Protein:Creatinine Ratio (UPCR) at Week 24 in the Blinded Treatment Period (Part B) | -34.86 Percent change from baseline |
Primary
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.
Time frame: From baseline up to 52 weeks after first dose in Part B
Population: All randomized participants in Part B
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label MMF + BMS-986165 | The Number of Participants Experiencing Averse Events in the Blinded Treatment Period (Part B) | 1 Participants |
Primary
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.
Time frame: From baseline up to 52 weeks after first dose in Part B
Population: All randomized participants in Part B
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label MMF + BMS-986165 | The Number of Participants With Abnormal Laboratory Parameters of Clinical Significance in the Blinded Treatment Period (Part B) | 0 Participants |
Primary
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.
Time frame: From baseline up to 52 weeks after first dose in Part B
Population: All randomized participants in Part B
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label MMF + BMS-986165 | The Number of Participants With Clinically Significant ECG Abnormalities in the Blinded Treatment Period (Part B) | 0 Participants |
Primary
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.
Time frame: From baseline up to 52 weeks after first dose in Part B
Population: All randomized participants in Part B
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open Label MMF + BMS-986165 | The Percent Change in Vital Sign Measurements in the Blinded Treatment Period (Part B) | Diastolic Blood Pressure(mmHg) | -3.45 Percent change from baseline |
| Open Label MMF + BMS-986165 | The Percent Change in Vital Sign Measurements in the Blinded Treatment Period (Part B) | Systolic Blood Pressure(mmHg | 5.22 Percent change from baseline |
| Open Label MMF + BMS-986165 | The Percent Change in Vital Sign Measurements in the Blinded Treatment Period (Part B) | Heart Rate(beats/min) | 16.87 Percent change from baseline |
| Open Label MMF + BMS-986165 | The Percent Change in Vital Sign Measurements in the Blinded Treatment Period (Part B) | Respiratory Rate(breaths/min) | 6.25 Percent change from baseline |
| Open Label MMF + BMS-986165 | The Percent Change in Vital Sign Measurements in the Blinded Treatment Period (Part B) | Temperature(C) | -1.35 Percent change from baseline |
Secondary
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.
Time frame: Week 24
Population: All randomized participants in Part B
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label MMF + BMS-986165 | The Number of Participants With Complete Renal Response (CRR) at Week 24 in the Blinded Treatment Period (Part B) | 0 Participants |
Secondary
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.
Time frame: Week 52
Population: All randomized participants in Part B
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label MMF + BMS-986165 | The Number of Participants With Complete Renal Response (CRR) at Week 52 in the Blinded Treatment Period (Part B) | 0 Participants |
Secondary
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.
Time frame: Week 24
Population: All randomized participants in Part B
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label MMF + BMS-986165 | 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) | 0 Participants |
Secondary
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.
Time frame: Week 52
Population: All randomized participants in Part B
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label MMF + BMS-986165 | 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) | 0 Participants |
Secondary
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.
Time frame: Week 24
Population: All randomized participants in Part B
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label MMF + BMS-986165 | The Number of Participants With Partial Renal Response (PRR) at Week 24 in the Blinded Treatment Period (Part B) | 0 Participants |
Secondary
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.
Time frame: Week 52
Population: All randomized participants in Part B
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label MMF + BMS-986165 | The Number of Participants With Partial Renal Response (PRR) at Week 52 in the Blinded Treatment Period (Part B) | 0 Participants |