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)

• ClinicalTrials.gov Identifier: NCT02592798
• Recruitment Status: Completed
• First Posted: October 30, 2015
• Results First Posted: March 5, 2021
• Last Update Posted: March 5, 2021
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: October 29, 2015
• First Posted Date: October 30, 2015
• Results First Submitted Date: January 19, 2021
• Results First Posted Date: March 5, 2021
• Last Update Posted Date: March 5, 2021
• Actual Study Start Date: March 9, 2016
• Actual Primary Completion Date: January 28, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 10, 2021)

Percentage of Participants in Renal Response at Day 113 [ 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) ]

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.

Original Primary Outcome Measures (submitted: October 29, 2015)

Proportion of subjects in Renal Response at Day 113 [ Time Frame: Day 113 ]

Proportion of subjects in Renal Response (reduction in baseline UPCR of ≥ 50% and to less than 3 with no worsening of baseline estimated glomerular filtration rate (eGFR: normal or ≥ 75% baseline if below normal at baseline)

Current Secondary Outcome Measures (submitted: February 10, 2021)

• 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) ]
• 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) ]
• Percentage of Participants Achieving Complete Remission at Day 113 [ 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) ]
  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 [ Time Frame: 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).
• Mean Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) at Day 113 - Pediatric Participants [ Time Frame: 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 [ 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) ]
  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 [ Time Frame: 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.
• Percentage of Participants With Positive Antibody Response Relative to Baseline [ 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 ]
  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 [ 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 ]
• 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 ]
• Maximum Observed Serum Concentration (Cmax) of Abatacept [ Time Frame: 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 [ Time Frame: From Day 85 to Day 113 in the Double Blind Period ]
• Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept [ Time Frame: Day 85 after first dose in the Double Blind Period ]

Original Secondary Outcome Measures (submitted: October 29, 2015)

• Mean change from baseline in Urine Protein to Creatinine Ratio (UPCR) at Day 113 [ Time Frame: Day 113 ]
• Mean change from baseline in serum albumin at Day 113 [ Time Frame: Day 113 ]
• Proportion of subjects achieving complete remission [ Time Frame: Day 113 ]
  Proportion of subjects achieving complete remission (UPCR ≤ 0.3 with Estimated glomerular filtration rate (eGFR): normal or ≥ 75% baseline if below normal at baseline) at Day 113
• Mean change in PROMIS measures [ Time Frame: Approximately 113 days ]
  Patient Reported Outcomes Measurement Information System (PROMIS)
• Safety measured by incidence, potential significance and clinical importance of AEs, SAEs, as determined by medical review of AE reports, vital sign measurements, ECGs and results of physical examination and laboratory tests [ Time Frame: Approximately 113 days ]
  Adverse Event (AE), Serious adverse event (SAE)
• Proportion of subjects with positive antibody response relative to baseline over time [ Time Frame: Approximately 113 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Nephrotic Syndrome
• Focal Segmental Glomerulosclerosis
• Minimal Change Disease

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

Study Arms

• 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
  Intervention: Drug: Abatacept
• 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
  Interventions:

  • Other: Normal Saline
  • Other: D5W

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 4, 2020): 36
• Original Estimated Enrollment (submitted: October 29, 2015): 90
• Actual Study Completion Date: January 28, 2020
• Actual Primary Completion Date: January 28, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02592798
• Other Study ID Numbers: IM101-566; 2015-005450-36 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: February 2021