Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Adults and Children 6 Years and Older With Excessive Loss of Protein in the Urine Due to Either Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
- Conditions
- Nephrotic SyndromeFocal Segmental GlomerulosclerosisMinimal Change Disease
- Interventions
- Registration Number
- NCT02592798
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is evaluate if abatacept is effective and safe in decreasing the level of protein loss in the urine in patients with excessive loss of protein in the urine (nephrotic syndrome) due to either focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). Candidates must have a prior kidney biopsy with either diagnosis. Another kidney biopsy will not be required as part of the study. Candidates must have failed or be intolerant of prior therapy for their kidney disease. The failed or intolerant therapy must include corticosteroids and at least one other drug. Candidates can be adults and children over the age of 6. Abatacept will be administered by venous infusion every 4 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
- Male and female subjects ages ≥ 6 years
- Subjects resistant to corticosteroids, calcineurin inhibitors (cyclosporine and tacrolimus), sirolimus, mycophenolate mofetil (MMF), mycophenolic acid (MPA), or cyclophosphamide or intolerant to at least 2 of these
- UPCR ≥ 3 at screening
- FSGS or MCD confirmed by renal biopsy
- eGFR ≥ 45 for children and adults
- Concomitant use of angiotensin-converting-enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) at stable doses for at least 2 weeks or have intolerance documented in the source documents maintained at the site
- Kidney diseases other than FSGS or MCD
- Collapsing FSGS
- Systemic lupus erythematosus
- Diabetes mellitus, both type 1 and type 2
- Clinically significant congestive heart failure
- Post renal transplantation, including relapsing post-transplant FSGS
- Body mass index (BMI): > 40 in subjects ≥ 18 years of age and ≥ 99% percentile for subjects < 18 years of age
Other protocol defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo D5W * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administer on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days Placebo Normal Saline * Double Blind Periods 1 and 2 (DB1 and DB2): Normal Saline or Dextrose 5% in Water (D5W) administer on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days Abatacept Abatacept * Double Blind Periods 1 and 2 (DB1 and DB2): Abatacept IV administered on Day 1, 15, 29 and then every 28 days until the end of the Double Blind Period. * Open Label Period (OLE): Abatacept IV administered every 28 days
- Primary Outcome Measures
Name Time Method Percentage of Participants in Renal Response at Day 113 From first dose to 113 days following first dose of the indicated period (113 days for Double-Blind Period, 226 days for Open Label Period) Renal Response is defined as the presence of all the following criteria:
PROTEINURIA: Reduction of baseline urine protein/creatinine ratio (UPCR) of \>= 50% and to less than 3.
RENAL FUNCTION: No worsening of baseline estimated glomerular filtration rate (eGFR) defined as within normal range if normal at baseline or ≥ 75% baseline value if below normal at baseline.
- Secondary Outcome Measures
Name Time Method Number of Participants Experiencing Adverse Events of Special Interest From first dose on day 1 to 56 days following last dose (approximately 330 days) Number of participants experiencing various types of Adverse Events of interest, including infections, malignancies, autoimmune disorders, and infusional related reactions.
Maximum Observed Serum Concentration (Cmax) of Abatacept Day 85 after first dose in the Double Blind Period Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 113 From baseline (measured at day 1 of study) to 113 days following first dose administered in the indicated treatment period (113 days for Double-Blind Period, 226 days for Open Label Period) Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants From first dose to 113 days after first dose in the Double Blind Period. Data collected on day 15, day 29, day 57, day 85 and day 113 Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept Day 85 after first dose in the Double Blind Period Percentage of Participants Achieving Complete Remission at Day 113 From first dose to 113 days following first dose of the indicated period (113 days for Double-Blind Period, 226 days for Open Label Period) Complete Remission is defined as the presence of all the following criteria:
PROTEINURIA: Urine protein/creatinine ratio (UPCR) ≤ 0.3. RENAL FUNCTION: No worsening of baseline estimated glomerular filtration rate (eGFR) defined as within normal range if normal at baseline or ≥ 75% baseline value if below normal at baseline.Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period PROMIS was used to capture patient reported outcomes relevant to participants with nephrotic syndrome. Mean change from baseline is reported for the following measurements:
Fatigue: Short From (SF) Fatigue v1.0 Peds 10a, composed of 10 questions, each one scored from 0 (Never) to 4 (Almost Always). Output presented as Total score, ranging from 0 (most desirable outcome) to 40 (least desirable outcome).
Pain Interference: SF Pain Interference v1.0 Peds 8a, ( measuring how much pain is interfering with daily activities). Composed of 8 questions, each one scored from 0 (Never) to 4 (Almost always). Output presented as Total score, ranging from 0 (most desirable outcome) to 32 (least desirable outcome).
Mobility: SF Physical Function-Mobility v1.0 Peds 8a, composed of 8 questions, each one scored from 0 (Not able to do) to 4 (With no trouble). Output presented as Total score, ranging from 0 (least desirable outcome) to 32 (most desirable outcome).Number of Participants Experiencing Adverse Events From first dose in the indicated period to 56 days following last dose in the indicated period (169 days for the Double-Blind Period, up to 337 days for the Cumulative Abatacept Safety Period) This outcome describes the number of participants experiencing various types of any grade Adverse Events (AEs).
The Cumulative Abatacept Safety Period starts at the time of the first dose of Abatacept (either in the Double-Blind Period or in the Open Label Period) and lasts 56 days after the last dose of AbataceptMinimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants From first dose to 113 days after first dose in the Double Blind Period. Data collected on day 15, day 29, day 57, day 85 and day 113 Mean Change From Baseline in Serum Albumine at Day 113 From baseline (measured at day 1 of the study) to 113 days following first dose administered in the indicated treatment period (113 days for Double-Blind Period, 226 days for Open Label Period) Area Under the Serum Concentration Time Curve Over a Dosing Interval (AUC(TAU)) of Abatacept From Day 85 to Day 113 in the Double Blind Period Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period PROMIS was used to capture patient reported outcomes relevant to participants with nephrotic syndrome. Mean change from baseline is reported for the following measurements:
Fatigue: Short From (SF) Fatigue v1.0 Adult 8a, composed of 8 questions, each one scored from 1 (Not at all) to 5 (Very much). Output presented as Total score, ranging from 8 (most desirable outcome) to 40 (least desirable outcome).
Pain Interference: SF Pain Interference v1.0 Adult 8a, (measuring how much pain is interfering with daily activities). Composed of 8 questions, each one scored from 1 (Not at all) to 5 (Very much). Output presented as Total score, ranging from 8 (most desirable outcome) to 40 (least desirable outcome).
Physical Function: SF Physical Function v1.2 Adult 8b, composed of 8 questions, each one scored from 1 (Without any difficulty) to 5 (Unable to do). Output presented as Total score, ranging from 8 (most desirable outcome) to 40 (least desirable outcome).Percentage of Participants With Positive Antibody Response Relative to Baseline From baseline (day 1) to 168 days following last dose (up to 15 months). Results at day 113 from first dose, day 56, day 84 and day 168 after last dose are presented A positive response relative to baseline is defined as a positive response at a post-baseline visit that has a titer value greater than the positive baseline titer value. If the baseline titer is missing or negative, any post-baseline positive titer value is considered a positive response relative to baseline.
Immunogenicity response is presented as the total of immunogenicity response for "CTLA4 and possibly Ig" and "Ig and/or Junction Region".
Trial Locations
- Locations (27)
Levine Children's Hospital
🇺🇸Charlotte, North Carolina, United States
Children's National Health System
🇺🇸Washington, District of Columbia, United States
Columbia University Medical Center (Cumc)
🇺🇸New York, New York, United States
Los Angeles Biomedical Research Institute
🇺🇸Torrance, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Brigham And Women'S Hosp Inc.
🇺🇸Boston, Massachusetts, United States
Boston Childrens Hospital
🇺🇸Boston, Massachusetts, United States
The Metro Health System
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Local Institution
🇺🇸Pittsburgh, Pennsylvania, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Nemours Childrens Hospital
🇺🇸Orlando, Florida, United States
Childrens Mercy Hospital
🇺🇸Kansas City, Missouri, United States
New York University Langone Medical Center
🇺🇸New York, New York, United States
University Of Miami Miller School Of Medicine
🇺🇸Miami, Florida, United States
Cincinnati Children'S Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Duke University
🇺🇸Durham, North Carolina, United States
The University Of Alabama At Birmingham
🇺🇸Birmingham, Alabama, United States
University of Alabama-Birmingham-Parent Account
🇺🇸Birmingham, Alabama, United States
University Of Colorado Denver
🇺🇸Aurora, Colorado, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
NIH Clinical Center - NIDDK
🇺🇸Bethesda, Maryland, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
University Of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Renal Disease Research Institute
🇺🇸Dallas, Texas, United States
University Of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States