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Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

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ClinicalTrials.gov Identifier: NCT01714817
Recruitment Status : Active, not recruiting
First Posted : October 26, 2012
Results First Posted : December 21, 2017
Last Update Posted : December 21, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of this study is to evaluate (Abatacept) for treatment of lupus nephritis when used on a background of Cellcept (mycophenolate) and prednisone (corticosteroids)

Condition or disease Intervention/treatment Phase
Lupus Nephritis Biological: BMS-188667 Drug: Mycophenolate mofetil Drug: Prednisone Biological: Placebo matching with BMS-188667 Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 695 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BMS-188667 (Abatacept) or Placebo on a Background of Mycophenolate Mofetil and Corticosteroids in the Treatment of Subjects With Active Class III or IV Lupus Nephritis
Actual Study Start Date : January 22, 2013
Primary Completion Date : November 21, 2016
Estimated Study Completion Date : May 18, 2018


Arms and Interventions

Arm Intervention/treatment
Experimental: BMS-188667 + Mycophenolate mofetil + Prednisone
BMS-188667 30 mg/kg injection by intravenous on Days 1,15, 29, and 57, followed by a weight-tiered dose approximating 10mg/kg injection by intravenous every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 weeks
Biological: BMS-188667
Other Name: Abatacept
Drug: Mycophenolate mofetil
Other Name: Cellcept
Drug: Prednisone
Placebo Comparator: Placebo + Mycophenolate mofetil + Prednisone
Placebo matching with BMS-188667 injection by intravenous on Days 1,15, 29, and 57, followed by every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 Weeks
Drug: Mycophenolate mofetil
Other Name: Cellcept
Drug: Prednisone Biological: Placebo matching with BMS-188667


Outcome Measures

Primary Outcome Measures :
  1. Proportion of Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period [ Time Frame: 365 days ]
    Number of participants achieving CR was divided by the total number of participants in that arm and expressed as a percentage. Complete Response (CR) defined as: eGFR is normal or no <85% of the baseline; eGFR based on mean creatinine value from day 358 and 365. Proteinuria: UPCR<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no >10 mg prednisone or equiv. for at least 28 days prior to assessment. Participants with >10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as having achieved CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use (Yes/No), race (Asian/ Black/Caucasian/Other) and baseline UPCR as a continuous variable.


Secondary Outcome Measures :
  1. Proportion of Nephrotic Participants in CR of Lupus Glomerulonephritis at Day 365 of the Double-blind Period [ Time Frame: 365 days ]
    Number of participants achieving CR was divided by total participants in that arm, expressed as a percentage. Nephrotic is defined as screening UPCR >=3.0 mg/mg (>=339mg/mmol). CR is defined the following criteria: eGFR is normal or no <85% of the baseline value; eGFR is based on mean creatinine value from day 358 and 365. Proteinuria: UPCR<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no >10 mg prednisone or equivalent for at least 28 days prior. Subjects with >10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use, race and baseline UPCR as a continuous variable.

  2. Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Nephrotic Participants [ Time Frame: Baseline and Day 365 ]
    Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in nephrotic participants

  3. Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Overall Population [ Time Frame: Baseline and Day 365 ]
    Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in the overall population

  4. Number of Participants With Ranked Outcome of CR, PR, and No Response at Day 365 of the Double-blind Period [ Time Frame: 365 days ]
  5. Median Time to Complete Response (CR) During Year 1 of the Double-blind Period in All Participants [ Time Frame: 365 days ]
  6. Median Time to Complete Response (CR) During Year 1 of the Double-blind Period in Nephrotic Participants [ Time Frame: 365 days ]
  7. Median Time to Partial Response (PR) During Year 1 of the Double-blind Period in All Participants [ Time Frame: 365 days ]
  8. Median Time to Partial Response (PR) During Year 1 of the Double-blind Period in Nephrotic Participants [ Time Frame: 365 days ]
  9. Adjusted Mean Change From Baseline in UPCR Over Time [ Time Frame: 365 days ]
  10. Median Percent Change From Baseline in UPCR Over Time [ Time Frame: 365 days ]
  11. Adjusted Mean Change From Baseline in eGFR Over Time [ Time Frame: 365 days ]
  12. Time to First Sustained Change to No Response During Year 1 of Double-blind Period [ Time Frame: 365 days ]
  13. Number of Participants With Sustained Change From Higher Level of Response to no Response During Year 1 of the Double-blind Period [ Time Frame: 365 days ]
  14. Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During Year 1 of the Double-blind Period [ Time Frame: From Day 1 to Day 365 (approximately 1 year) ]
  15. Number of Participants With Any Adverse Events (AEs) [ Time Frame: From Day 1 up to 56 days post last dose in Year 1 of the double-blind period ]
  16. Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion [ Time Frame: Days 1, 15, 29, 57, 85, 113,169, 281, 337, and 365 ]
  17. Cmax (ug/mL): Maximum Observed Serum Concentration Following Subjects Receiving Active Abatacept IV [ Time Frame: at 1 hour post Day 1 dose and 30 minutes post Day 337 dose ]
  18. AUC (TAU) (ug*h/mL): Area Under the Serum Concentration Time Curve Over a Dosing Interval [ Time Frame: Days 337 to 365 ]
  19. Summary Statistics for Systolic Blood Pressure [ Time Frame: Day 1 to Day 365 ]
  20. Summary Statistics for Diastolic Blood Pressure [ Time Frame: Day 1 to Day 365 ]
  21. Summary Statistics for Heart Rate [ Time Frame: Day 1 to Day 365 ]
  22. Mean Change From Baseline in Laboratory Analytes During Year 1 of the Double-blind Period [ Time Frame: 365 days ]
  23. Number of Participants With Marked Hematology Laboratory Abnormalities [ Time Frame: From Baseline up to 56 days post last dose in Year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier. ]
  24. Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities [ Time Frame: From Baseline up to 56 days post last dose in Year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier. ]
  25. Number of Participants With Marked Electrolyte Laboratory Abnormalities [ Time Frame: From Baseline up to 56 days post last dose in Year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier. ]
  26. Number of Participants With Marked Urinalysis Laboratory Abnormalities [ Time Frame: From Baseline up to 56 days post last dose in Year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier. ]
  27. Number of Participants With Marked Chemistry Laboratory Abnormalities [ Time Frame: From Baseline up to 56 days post last dose in Year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier. ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

For additional information please contact the BMS Lupus Nephritis Clinical Trial Matching Service at 855-56-LUPUS. Please visit www.BMSStudyConnect.com for more information on clinical trial participation.

Note: Subjects > 16 are eligible for enrollment at selected centers

Inclusion Criteria:

  • Potential subjects must have active lupus nephritis
  • Biopsy within 12 months prior to screening visit indicating active Class 3 or 4 proliferative lupus glomerulonephritis (lupus effecting your kidney)
  • Urine protein creatinine ratio (UPCR) ≥ 1 at Screening
  • Serum creatinine ≤ 3 mg/dL (ie, ≤ 265 micromol/L)
  • There must also be evidence of active disease within 3 months of Screening, based on at least one of the following:

    • Worsening of lupus nephritis OR
    • UPCR ≥ 3 at Screening OR
    • Active urine sediment OR
    • Biopsy within 3 months prior to screening visit indicating active Class 3 or Class 4 active proliferative lupus glomerulonephritis

Inclusion Criteria for the Long-Term Extension Period:

  • Signed Written Informed Consent
  • Subjects who achieve a complete or partial renal response after completing 2 years of double-blind treatment

Exclusion Criteria:

  • Systemic Lupus Erythematosus (SLE) must be the primary/main autoimmune diagnosis
  • Current symptoms of severe, progressive, or uncontrolled non-SLE related renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, or other concomitant medical conditions that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study
  • Significant active Central nervous system (CNS) lupus with the exception of fatigue or mild stable cognitive
  • Subjects who are diagnosed as end-stage renal disease or whose kidney damage is too significant and irreversible
Contacts and Locations

Information from the National Library of Medicine

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): NCT01714817


  Show 128 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01714817     History of Changes
Other Study ID Numbers: IM101-291
2012-000714-11 ( EudraCT Number )
First Posted: October 26, 2012    Key Record Dates
Results First Posted: December 21, 2017
Last Update Posted: December 21, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Nephritis
Lupus Nephritis
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Prednisone
Mycophenolic Acid
Abatacept
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents