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)

Nephrotic Syndrome Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02592798
• Other study ID #: IM101-566
• Secondary ID: 2015-005450-36
• Status: Completed
• Phase: Phase 2
• Start date: March 9, 2016
• Est. completion date: January 28, 2020

Study information

• Verified date: February 2021
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: January 28, 2020
• Est. primary completion date: January 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Focal Segmental Glomerulosclerosis
• Glomerulosclerosis, Focal Segmental
• Minimal Change Disease
• Nephrosis
• Nephrosis, Lipoid
• Nephrotic Syndrome
• Syndrome

Intervention

Drug:
• Abatacept
Abatacept IV administered on Day 1, 15, 29 and then every 28 days

Other:
• Normal Saline
Normal Saline administer on Day 1, 15, 29 and then every 28 days
• D5W
Dextrose 5% in Water (D5W) administered on Day 1, 15, 29 and then every 28 days

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	University Of Colorado Denver	Aurora	Colorado
United States	NIH Clinical Center - NIDDK	Bethesda	Maryland
United States	The University Of Alabama At Birmingham	Birmingham	Alabama
United States	University of Alabama-Birmingham-Parent Account	Birmingham	Alabama
United States	Boston Childrens Hospital	Boston	Massachusetts
United States	Brigham And Women'S Hosp Inc.	Boston	Massachusetts
United States	Levine Children's Hospital	Charlotte	North Carolina
United States	Cincinnati Children'S Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Metro Health System	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Renal Disease Research Institute	Dallas	Texas
United States	University Of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Childrens Mercy Hospital	Kansas City	Missouri
United States	Loyola University Medical Center	Maywood	Illinois
United States	University Of Miami Miller School Of Medicine	Miami	Florida
United States	Columbia University Medical Center (Cumc)	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	Nemours Childrens Hospital	Orlando	Florida
United States	University Of Pennsylvania	Philadelphia	Pennsylvania
United States	Local Institution	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Los Angeles Biomedical Research Institute	Torrance	California
United States	Children's National Health System	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	Maximum Observed Serum Concentration (Cmax) of Abatacept		Day 85 after first dose in the Double Blind Period
Secondary	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
Secondary	Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept		Day 85 after first dose in the Double Blind Period

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