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)

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)

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.

Study Overview

• Status: Completed
• Conditions: Focal Segmental Glomerulosclerosis; Nephrotic Syndrome; Minimal Change Disease
• Intervention / Treatment: Drug: Abatacept; Other: Normal Saline; Other: D5W

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • The University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35294
      • University of Alabama-Birmingham-Parent Account
  • California
    • Torrance, California, United States, 90502
      • Los Angeles Biomedical Research Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Health System
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
    • Orlando, Florida, United States, 32827
      • Nemours Childrens Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322-1015
      • Emory University
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • NIH Clinical Center - NIDDK
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Childrens Hospital
    • Boston, Massachusetts, United States, 02115
      • Brigham And Women'S Hosp Inc.
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Childrens Mercy Hospital
  • New York
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center (CUMC)
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Levine Children's Hospital
    • Durham, North Carolina, United States, 27701
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44109
      • The Metro Health System
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Local Institution
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75235
      • Renal Disease Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Abatacept; Abatacept IV administered on Day 1, 15, 29 and then every 28 days
Placebo Comparator: Placebo; 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	Other: Normal Saline; Normal Saline administer on Day 1, 15, 29 and then every 28 days; Other: D5W; Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days; Other Names: 5% Dextrose in Water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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 Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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.	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)
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).	From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period
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).	From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period
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	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)
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.	From first dose on day 1 to 56 days following last dose (approximately 330 days)
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".	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
Minimum 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
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
Maximum Observed Serum Concentration (Cmax) of Abatacept		Day 85 after first dose in the Double Blind 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
Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept		Day 85 after first dose in the Double Blind Period

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2016
• Primary Completion (Actual): January 28, 2020
• Study Completion (Actual): January 28, 2020

Study Registration Dates

• First Submitted: October 29, 2015
• First Submitted That Met QC Criteria: October 29, 2015
• First Posted (Estimate): October 30, 2015

Study Record Updates

• Last Update Posted (Actual): March 5, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Nephritis; Glomerulonephritis; Syndrome; Glomerulosclerosis, Focal Segmental; Nephrotic Syndrome; Nephrosis; Nephrosis, Lipoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: IM101-566; 2015-005450-36 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No