Clinical Trial Results:
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
Summary
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EudraCT number |
2018-004142-42 |
Trial protocol |
DE BE NL CZ ES GB IT |
Global end of trial date |
17 Sep 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Oct 2022
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First version publication date |
04 Oct 2022
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
IM011-073
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03943147 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bristol-Myers Squibb
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Sponsor organisation address |
Chaussée de la Hulpe 185, Brussels, Belgium, 1170
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Public contact |
EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
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Scientific contact |
Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Oct 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Sep 2021
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main objectives are to assess the safety and tolerability of BMS-986165 in participants with lupus nephritis and to evaluate the efficacy of BMS-986165 compared with placebo with regard to proteinuria.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Jul 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
China: 1
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Country: Number of subjects enrolled |
Korea, Republic of: 1
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Country: Number of subjects enrolled |
Mexico: 2
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Country: Number of subjects enrolled |
Russian Federation: 1
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
Taiwan: 1
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Country: Number of subjects enrolled |
United Kingdom: 2
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Country: Number of subjects enrolled |
United States: 7
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Worldwide total number of subjects |
16
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EEA total number of subjects |
1
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
16
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||
Pre-assignment
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Screening 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. | ||||||||||||||||||
Period 1
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Period 1 title |
Open-Label MMF Run-in (Part A)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Arms
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Arm title
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Open Label MMF | ||||||||||||||||||
Arm description |
All study participants receive Mycophenolate Mofetil (MMF) at a dose of 1.5 to 3.0 g/day for 12 weeks. 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 | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Mycophenolate Mofetil (MMF)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dose of 1.5 to 3.0 g/day
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Period 2
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Period 2 title |
Blinded Treatment (Part B)
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Open Label MMF | ||||||||||||||||||
Arm description |
After participants receive Mycophenolate Mofetil (MMF) at a dose of 1.5 to 3.0 g/day for 12 weeks in Part A, 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. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Mycophenolate Mofetil (MMF)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dose of 1.5 to 3.0 g/day
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Arm title
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Open Label MMF + BMS-986165 | ||||||||||||||||||
Arm description |
After participants receive Mycophenolate Mofetil (MMF) at a dose of 1.5 to 3.0 g/day for 12 weeks 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. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
BMS-986165
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
6 mg twice daily (BID)
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Investigational medicinal product name |
Mycophenolate Mofetil (MMF)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dose of 1.5 to 3.0 g/day
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Baseline characteristics reporting groups
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Reporting group title |
Open Label MMF
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Reporting group description |
All study participants receive Mycophenolate Mofetil (MMF) at a dose of 1.5 to 3.0 g/day for 12 weeks. 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Open Label MMF
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Reporting group description |
All study participants receive Mycophenolate Mofetil (MMF) at a dose of 1.5 to 3.0 g/day for 12 weeks. 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 | ||
Reporting group title |
Open Label MMF
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Reporting group description |
After participants receive Mycophenolate Mofetil (MMF) at a dose of 1.5 to 3.0 g/day for 12 weeks in Part A, 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. | ||
Reporting group title |
Open Label MMF + BMS-986165
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Reporting group description |
After participants receive Mycophenolate Mofetil (MMF) at a dose of 1.5 to 3.0 g/day for 12 weeks 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. |
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End point title |
The Number of Participants Experiencing Averse Events in the Blinded Treatment Period (Part B) [1] | ||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
From baseline up to 52 weeks after first dose in Part B
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics planned for this endpoint |
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No statistical analyses for this end point |
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End point title |
The Number of Participants with Clinically Significant ECG Abnormalities in the Blinded Treatment Period (Part B) [2] | ||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
From baseline up to 52 weeks after first dose in Part B
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics planned for this endpoint |
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No statistical analyses for this end point |
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End point title |
The Percent Change in Vital Sign Measurements in the Blinded Treatment Period (Part B) [3] | ||||||||||||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
From baseline up to 52 weeks after first dose in Part B
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics planned for this endpoint |
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No statistical analyses for this end point |
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End point title |
The Number of Participants with Abnormal Laboratory Parameters of Clinical Significance in the Blinded Treatment Period (Part B) [4] | ||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
From baseline up to 52 weeks after first dose in Part B
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics planned for this endpoint |
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No statistical analyses for this end point |
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End point title |
Percent Change from Baseline in 24-hour Urine Protein:Creatinine Ratio (UPCR) at Week 24 in the Blinded Treatment Period (Part B) [5] | ||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
Week 24
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics planned for this endpoint |
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No statistical analyses for this end point |
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End point title |
The Number of Participants with Partial Renal Response (PRR) at Week 24 in the Blinded Treatment Period (Part B) | ||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Week 24
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No statistical analyses for this end point |
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End point title |
The Number of Participants with Complete Renal Response (CRR) at Week 24 in the Blinded Treatment Period (Part B) | ||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Week 24
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No statistical analyses for this end point |
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End point title |
The Number of Participants with Partial Renal Response (PRR) at Week 52 in the Blinded Treatment Period (Part B) | ||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Week 52
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No statistical analyses for this end point |
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End point title |
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) | ||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Week 24
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No statistical analyses for this end point |
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End point title |
The Number of Participants with Complete Renal Response (CRR) at Week 52 in the Blinded Treatment Period (Part B) | ||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Week 52
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No statistical analyses for this end point |
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End point title |
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) | ||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Week 52
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
All-cause mortality was assessed from first dose to study completion (up to approximately 26 months). SAEs and Other AEs were assessed from first dose to 30 days following last dose (up to approximately 16 months)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
Open Label MMF
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Reporting group description |
All study participants receive Mycophenolate Mofetil (MMF) at a dose of 1.5 to 3.0 g/day for 12 weeks in Part A. 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Open Label MMF + BMS-986165
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Reporting group description |
All participants that met randomization criteria for Part B. Participants received 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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20 Sep 2019 |
Modified several inclusion and exclusion criteria. Clarified that subjects may begin treatment with non-study-supplied MMF during the screening period. |
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06 Aug 2020 |
Added a 52-week Long-term Extension (LTE) period. Modified study objectives and endpoints, including new primary and secondary efficacy endpoints. Updated statistical considerations based on updated endpoints and addition of LTE period. Modified inclusion/exclusion criteria details and previous and concomitant therapy allowed and prohibited. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Due to low enrollment, the Sponsor chose to terminate the study on 01-Jul-2021. There is limited data available therefore no formal statistical analyses of endpoints were conducted. |