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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)

Primary Purpose

Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, Minimal Change Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Abatacept
Normal Saline
D5W
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nephrotic Syndrome

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • The University Of Alabama At Birmingham
  • University of Alabama-Birmingham-Parent Account
  • Los Angeles Biomedical Research Institute
  • University Of Colorado Denver
  • Children's National Health System
  • University Of Miami Miller School Of Medicine
  • Nemours Childrens Hospital
  • Emory University
  • Loyola University Medical Center
  • NIH Clinical Center - NIDDK
  • Boston Childrens Hospital
  • Brigham And Women'S Hosp Inc.
  • University of Michigan
  • Mayo Clinic
  • Childrens Mercy Hospital
  • New York University Langone Medical Center
  • Columbia University Medical Center (Cumc)
  • Levine Children's Hospital
  • Duke University
  • Cincinnati Children'S Hospital Medical Center
  • The Metro Health System
  • Cleveland Clinic
  • The Ohio State University Wexner Medical Center
  • University Of Pennsylvania
  • Local Institution
  • Renal Disease Research Institute
  • University Of Texas Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Abatacept

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Percentage of Participants in Renal Response at Day 113
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

Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 113
Mean Change From Baseline in Serum Albumine at Day 113
Percentage of Participants Achieving Complete Remission at Day 113
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 - Adult Participants
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).
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants
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
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 Abatacept
Number of Participants Experiencing Adverse Events of Special Interest
Number of participants experiencing various types of Adverse Events of interest, including infections, malignancies, autoimmune disorders, and infusional related reactions.
Percentage of Participants With Positive Antibody Response Relative to Baseline
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".
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants
Maximum Observed Serum Concentration (Cmax) of Abatacept
Area Under the Serum Concentration Time Curve Over a Dosing Interval (AUC(TAU)) of Abatacept
Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept

Full Information

First Posted
October 29, 2015
Last Updated
February 10, 2021
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT02592798
Brief Title
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)
Official Title
A Phase II Randomized, Placebo-Controlled, Double-Blind, Parallel Arms, Pilot Study to Evaluate the Efficacy and Safety of Intravenous Abatacept in Treatment Resistant Nephrotic Syndrome (Focal Segmental Glomerulosclerosis/ Minimal Change Disease)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
March 9, 2016 (Actual)
Primary Completion Date
January 28, 2020 (Actual)
Study Completion Date
January 28, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, Minimal Change Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Abatacept
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Abatacept
Intervention Description
Abatacept IV administered on Day 1, 15, 29 and then every 28 days
Intervention Type
Other
Intervention Name(s)
Normal Saline
Intervention Description
Normal Saline administer on Day 1, 15, 29 and then every 28 days
Intervention Type
Other
Intervention Name(s)
D5W
Other Intervention Name(s)
5% Dextrose in Water
Intervention Description
Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days
Primary Outcome Measure Information:
Title
Percentage of Participants in Renal Response at Day 113
Description
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.
Time Frame
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)
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 113
Time Frame
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)
Title
Mean Change From Baseline in Serum Albumine at Day 113
Time Frame
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)
Title
Percentage of Participants Achieving Complete Remission at Day 113
Description
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.
Time Frame
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)
Title
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants
Description
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).
Time Frame
From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period
Title
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants
Description
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).
Time Frame
From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period
Title
Number of Participants Experiencing Adverse Events
Description
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 Abatacept
Time Frame
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)
Title
Number of Participants Experiencing Adverse Events of Special Interest
Description
Number of participants experiencing various types of Adverse Events of interest, including infections, malignancies, autoimmune disorders, and infusional related reactions.
Time Frame
From first dose on day 1 to 56 days following last dose (approximately 330 days)
Title
Percentage of Participants With Positive Antibody Response Relative to Baseline
Description
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".
Time Frame
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
Title
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants
Time Frame
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
Title
Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants
Time Frame
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
Title
Maximum Observed Serum Concentration (Cmax) of Abatacept
Time Frame
Day 85 after first dose in the Double Blind Period
Title
Area Under the Serum Concentration Time Curve Over a Dosing Interval (AUC(TAU)) of Abatacept
Time Frame
From Day 85 to Day 113 in the Double Blind Period
Title
Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept
Time Frame
Day 85 after first dose in the Double Blind Period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
The University Of Alabama At Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of Alabama-Birmingham-Parent Account
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Los Angeles Biomedical Research Institute
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
University Of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's National Health System
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University Of Miami Miller School Of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Nemours Childrens Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322-1015
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
NIH Clinical Center - NIDDK
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Boston Childrens Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Brigham And Women'S Hosp Inc.
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Childrens Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
New York University Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Columbia University Medical Center (Cumc)
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Levine Children's Hospital
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27701
Country
United States
Facility Name
Cincinnati Children'S Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
Country
United States
Facility Name
The Metro Health System
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
The Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University Of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Local Institution
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Renal Disease Research Institute
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
University Of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35230699
Citation
Azukaitis K, Palmer SC, Strippoli GF, Hodson EM. Interventions for minimal change disease in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2022 Mar 1;3(3):CD001537. doi: 10.1002/14651858.CD001537.pub5.
Results Reference
derived
PubMed Identifier
35224732
Citation
Hodson EM, Sinha A, Cooper TE. Interventions for focal segmental glomerulosclerosis in adults. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD003233. doi: 10.1002/14651858.CD003233.pub3.
Results Reference
derived
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls

Learn more about this trial

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)

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