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)
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| ClinicalTrials.gov Identifier: NCT02592798 |
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Recruitment Status :
Completed
First Posted : October 30, 2015
Results First Posted : March 5, 2021
Last Update Posted : March 5, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Nephrotic Syndrome Focal Segmental Glomerulosclerosis Minimal Change Disease | Drug: Abatacept Other: Normal Saline Other: D5W | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 36 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | March 9, 2016 |
| Actual Primary Completion Date : | January 28, 2020 |
| Actual Study Completion Date : | January 28, 2020 |
| Arm | Intervention/treatment |
|---|---|
Experimental: Abatacept
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Drug: Abatacept
Abatacept IV administered on Day 1, 15, 29 and then every 28 days |
Placebo Comparator: Placebo
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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 |
- 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.
- 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 ]
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| Ages Eligible for Study: | 6 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02592798
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| Study Director: | Bristol Myers Squibb | Bristol-Myers Squibb |
Documents provided by Bristol-Myers Squibb:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT02592798 |
| Other Study ID Numbers: |
IM101-566 2015-005450-36 ( EudraCT Number ) |
| First Posted: | October 30, 2015 Key Record Dates |
| Results First Posted: | March 5, 2021 |
| Last Update Posted: | March 5, 2021 |
| Last Verified: | February 2021 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Nephrotic Syndrome Nephrosis Glomerulosclerosis, Focal Segmental Nephrosis, Lipoid Syndrome Disease Pathologic Processes Kidney Diseases Urologic Diseases Glomerulonephritis |
Nephritis Abatacept Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |