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Completed

NCT Number: 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)

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.

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Key information

Age range

6 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The University Of Alabama At Birmingham, Birmingham, Alabama, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Abatacept

Drug

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

Normal Saline

Other

Normal Saline administer on Day 1, 15, 29 and then every 28 days

D5W

Other

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

Other names: 5% Dextrose in Water

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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)

  2. 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)

  3. 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.

  4. 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).

  5. 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).

  6. 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

  7. 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.

  8. 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".

  9. 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

  10. 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

  11. Maximum Observed Serum Concentration (Cmax) of Abatacept

    Time frame: Day 85 after first dose in the Double Blind Period

  12. 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

  13. Time to Reach Peak Serum Concentration (Tmax(h)) of Abatacept

    Time frame: Day 85 after first dose in the Double Blind Period

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study 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)

Important dates

Study start
2016
Primary completion
2020
Study completion
2020
First posted
Oct 30, 2015
Registry last updated
Mar 5, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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