Clinical trial NCT02592798: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nephrotic Syndrome
Focal Segmental Glomerulosclerosis
Minimal Change Disease
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2015-10-30
Enrollment: 36
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants in Renal Response at Day 113
timeFrame: 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 outcomes:
measure: Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 113
timeFrame: 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)
measure: Mean Change From Baseline in Serum Albumine at Day 113
timeFrame: 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)
measure: Percentage of Participants Achieving Complete Remission at Day 113
timeFrame: 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)
measure: Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Adult Participants
timeFrame: From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period
measure: Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants
timeFrame: From baseline (measured at day 1 of study) to 113 days following first dose administered in the Double-Blind Period
measure: Number of Participants Experiencing Adverse Events
timeFrame: 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)
measure: Number of Participants Experiencing Adverse Events of Special Interest
timeFrame: From first dose on day 1 to 56 days following last dose (approximately 330 days)
measure: Percentage of Participants With Positive Antibody Response Relative to Baseline
timeFrame: 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
measure: Minimum Blood Plasma Concentration (Cmin) of Abatacept - Adult Participants
timeFrame: 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
measure: Minimum Blood Plasma Concentration (Cmin) of Abatacept - Pediatric Participants
timeFrame: 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
measure: Maximum Observed Serum Concentration (Cmax) of Abatacept
timeFrame: Day 85 after first dose in the Double Blind Period
measure: Area Under the Serum Concentration Time Curve Over a Dosing Interval (AUC(TAU)) of Abatacept
timeFrame: From Day 85 to Day 113 in the Double Blind Period
measure: Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept
timeFrame: Day 85 after first dose in the Double Blind Period
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University Of Alabama At Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama-Birmingham-Parent Account
state: Alabama
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute
state: California
city: Aurora
country: United States
facility: University Of Colorado Denver
state: Colorado
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
city: Miami
country: United States
facility: University Of Miami Miller School Of Medicine
state: Florida
city: Orlando
country: United States
facility: Nemours Childrens Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Bethesda
country: United States
facility: NIH Clinical Center - NIDDK
state: Maryland
city: Boston
country: United States
facility: Boston Childrens Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham And Women'S Hosp Inc.
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Childrens Mercy Hospital
state: Missouri
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center (Cumc)
state: New York
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children'S Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: The Metro Health System
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University Of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Local Institution
state: Pennsylvania
city: Dallas
country: United States
facility: Renal Disease Research Institute
state: Texas
city: Dallas
country: United States
facility: University Of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol Myers Squibb
role: STUDY_DIRECTOR
References:
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.
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.