Clinical trial NCT00430677: Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis
Official title: A Phase II/III Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept Versus Placebo on a Background of Mycophenolate Mofetil and Glucocorticosteroids in Subjects With Active Proliferative Glomerulonephritis Due to Systemic Lupus Erythematosus (SLE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-02-02
Enrollment: 423
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical research study is to learn if addition of abatacept is safe and improves the effectiveness of treatment of patients with active lupus nephritis who are also taking mycophenolate mofetil (MMF) and corticosteroids.

Detailed description: Double Blind Period: Treatment, Parallel Assignment, Double Blind (Subject, Investigator), Randomized, Active Control, Safety/Efficacy Study

Open Label Period: Prevention, Single Group Assignment, Open Label, Uncontrolled, Safety/Efficacy Study

Eligibility criteria: Inclusion Criteria:

* Systemic Lupus Erythematosus (SLE) as defined by meeting at least 4 of the 11 classification criteria of the American College of Rheumatology for the classification of Systemic Lupus Erythematosus, either sequentially or coincident. The 4 criteria need not be present at study entry
* Renal biopsy within 12 months prior to screening visit indicating active proliferative lupus glomerulonephritis (met ISN/RPS Class III or IV classification criteria \[2003\], excluding Class III \[C\], IV-S \[C\] and IV-G \[C\], or the World Health Organization Class III or IV classification criteria \[1982\], excluding Class IIIc, IVd). If the renal biopsy was performed \>3 months but ≤12 months prior to screening visit, at least 1 of the following 3 serologies (performed locally) must have been abnormal prior to screening visit: complement (C3 or C4) level below normal range OR anti-dsDNA \>upper limit of normal range.
* A stable serum creatinine ≤3 mg/dL

Exclusion Criteria:

* Subjects with a rise in serum creatinine of ≥1 mg/dL within 1 month prior to the screening visit
* Subjects with drug-induced SLE, as opposed to idiopathic SLE
* Subjects with severe, unstable and/or progressive Central nervous system (CNS) lupus
* Subjects with autoimmune disease other than SLE as their main diagnosis (e.g.; Rheumatoid arthritis (RA), Multiple Sclerosis \[MS\])
* Subjects who have received treatment with cyclophosphamide within 3 months of randomization (Day 1).
* Subjects who have received treatment with rituximab \< 6 months prior to the screening visit

Primary outcomes:
measure: Time to First Confirmed Complete Renal Response (CRR) During the Short-term (Double-blind) Period
timeFrame: Day 1 (randomization) to 12 months.
Secondary outcomes:
measure: Number of Participants With Confirmed Complete Renal Response (CRR) During Short-term Period
timeFrame: Day 1 to 12 months
measure: Participants Achieving a Confirmed Complete Renal Response (CRR) at Month 12 During Short-term Period
timeFrame: At Month 12 from Day 1
measure: Time to Achieve First Confirmed Renal Improvement (RI) During Short-term Period (as Determined by Kaplan-Meier Methodology)
timeFrame: Day 1 (randomization) to 12 months.
measure: Participants Achieving Renal Improvement (RI) or CRR at Month 12 During Short-term Period
timeFrame: At Month 12 from Day 1
measure: Number of Months CRR Was Maintained During Short-term Period
timeFrame: Day 1 (randomization) to 12 Months
measure: Baseline Renal Function Over Time During Short-term Period
timeFrame: Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365
measure: Change in Renal Function From Baseline Over Time During Short-term Period
timeFrame: Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365
measure: Baseline and Post Baseline Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index During Short-term Period
timeFrame: Baseline (Day 1), Post baseline (Month 12 or 28 days after last dose)
measure: Number of Participants Achieving Renal Response (RR) at Month 12 During Short-term Period
timeFrame: Month 12
measure: Change in SLICC/ACR Damage Index From Baseline During Short-term Period
timeFrame: Baseline (Day 1), Postbaseline (Month 12 or 28 days after last dose)
measure: Baseline Physical Component Summary of the Short Form (SF)-36 During Short-term Period
timeFrame: Baseline (Day 1), Days 85, 169, 253, and 365
measure: Change From Baseline in Physical Component Summary of the SF-36 During Short-term Period
timeFrame: Baseline (Day 1), Days 85, 169, 253, and 365
measure: Baseline Mental Component Summary of the Short SF-36 During Short-term Period
timeFrame: Baseline (Day 1), Days 85, 169, 253, and 365
measure: Change From Baseline in Mental Component Summary of the SF-36 During Short-term Period
timeFrame: Baseline (Day 1), Days 85, 169, 253, and 365
measure: Baseline Fatigue as Measured by the Fatigue Visual Analog Scale During Short-term Period
timeFrame: Baseline (Day 1), Days 85, 169, 253, and 365
measure: Change in Fatigue From Baseline as Measured by the Fatigue Visual Analog Scale During Short-term Period
timeFrame: Baseline (Day 1), Days 85, 169, 253, and 365
measure: Baseline Fatigue as Measured by Fatigue Severity Scale-Krupp During Short-term Period
timeFrame: Baseline (Day 1), Days 85, 169, 253, and 365
measure: Change in Fatigue From Baseline as Measured by Fatigue Severity Scale-Krupp During Short-term Period
timeFrame: Baseline (Day 1), Days 85, 169, 253, and 365
measure: Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs Reported During the Short-term Period
timeFrame: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
measure: Participants With AEs of Special Interest During the Short-term Period
timeFrame: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
measure: Participants With Marked Hematology Abnormalities During the Short-term Period
timeFrame: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
measure: Participants With Marked Laboratory Abnormalities During the Short-term Period
timeFrame: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
measure: Participants With Marked Liver and Kidney Function Abnormalities During the Short-term Period
timeFrame: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
measure: Participants With Marked Abnormalities Urinalysis During the Short-term Period
timeFrame: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
measure: Vital Signs Summary During the Short-term Period: Systolic Blood Pressure (SBP)
timeFrame: 0 - 12 Months
measure: Vital Signs Summary During the Short-term Period: Diastolic Blood Pressure (DBP)
timeFrame: 0 - 12 Months
measure: Vital Signs Summary During the Short-term Period: Heart Rate
timeFrame: 0 - 12 Months
measure: Vital Signs Summary During the Short-term Period: Temperature
timeFrame: 0 - 12 Months
measure: Number of Participants With Positive Abatacept-induced Responses (ECL Method) Over Time During the Short-term Period
timeFrame: Day 169, Day 365
measure: Baseline Quantitative Immunoglobulins During the Short-term Period
timeFrame: Baseline (Day 1)
measure: Change in Quantitative Immunoglobulin From Baseline During Short-term Period
timeFrame: Day 365
measure: Number of Participants Achieving Complete Response by ACCESS Definition
timeFrame: End of short-term period (Day 365) to termination of the long-term extension period
measure: Number of Participants Achieving Patient Response of Complete or Partial Response, Based on the June 2010 Food and Drug Administration Guidance Document for Lupus Nephritis
timeFrame: At Day 365 (end of Short-term Period) and Day 645
measure: Mean Change From Baseline in SLICC/ACR Damage Index
timeFrame: Day 365 to termination of the long-term extension phase
measure: Number of Participants With Death, Serious Adverse Events (SAE), Treatment-related Adverse Events SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs During Long-term Extension Period
timeFrame: From start of study drug in long-term period (Day 365) to up to 56 days after the last dose of the long-term extension (LTE). Deaths in LTE reported to >56 days post last dose.
measure: Number of Participants With a Treatment-emergent Seropositive Result During the Long-term Extension Period
timeFrame: Day 365 to end of long-term extension period
measure: Number of Participants Achieving Renal Response
timeFrame: At Day 365 (end of short-term period) and Day 645
measure: Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period
timeFrame: From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period
measure: Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued)
timeFrame: From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period
measure: Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued)
timeFrame: From start of study drug on Day 365 to up to 56 days after last dose in the long-term extension period
Other outcomes:
measure: Number of Participants Achieving Patient Response (PR) at Month 12 During the Short-term Period
timeFrame: Month 12
Locations:
city: Birmingham
country: United States
facility: University Of Alabama At Birmingham
state: Alabama
city: Tucson
country: United States
facility: Arizona Arthritis Center
state: Arizona
city: Los Angeles
country: United States
facility: Wallace Rheumatic Study Center
state: California
city: Kansas City
country: United States
facility: University Of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Boston University School Of Medicine
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Brooklyn
country: United States
facility: Suny Downstate Medical Center
state: New York
city: Lake Success
country: United States
facility: Northshore Lij Health System
state: New York
city: Manhasset
country: United States
facility: The Feinstein Institute For Medical Research
state: New York
city: Syracuse
country: United States
facility: Suny Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: University Of North Carolina At Chapel Hill
state: North Carolina
city: Oklahoma City
country: United States
facility: Ok Medical Research Foundation
state: Oklahoma
city: Knoxville
country: United States
facility: Rheumatology Consultants Pllc
state: Tennessee
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Ciudad Autonoma De Buenos Aire
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Cordoba
country: Argentina
facility: Local Institution
city: Tucuman
country: Argentina
facility: Local Institution
city: Liverpool
country: Australia
facility: Local Institution
state: New South Wales
city: Clayton
country: Australia
facility: Local Institution
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution
state: Victoria
city: Parkville
country: Australia
facility: Local Institution
state: Victoria
city: Bruxelles
country: Belgium
facility: Local Institution
city: Leuven
country: Belgium
facility: Local Institution
city: Goiania
country: Brazil
facility: Local Institution
state: Goias
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Rio De Janeiro
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Winnipeg
country: Canada
facility: Local Institution
state: Manitoba
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Quebec
country: Canada
facility: Local Institution
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Guangzhou
country: China
facility: Local Institution
state: Guangdong
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Xi'an
country: China
facility: Local Institution
state: Shanxi
city: Creteil Cedex
country: France
facility: Local Institution
city: Paris Cedex 13
country: France
facility: Local Institution
city: Strasbourg Cedex
country: France
facility: Local Institution
city: Toulouse Cedex 4
country: France
facility: Local Institution
city: Hong Kong
country: Hong Kong
facility: Local Institution
city: Gujarat
country: India
facility: Local Institution
state: Ahmedabad
city: Secunderabad
country: India
facility: Local Institution
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Local Institution
state: Gujarat
city: Nadiad
country: India
facility: Local Institution
state: Gujarat
city: Bangalore
country: India
facility: Local Institution
state: Karnataka
city: Bangalore
country: India
facility: Local Institution
state: Karnataka
city: Kochi
country: India
facility: Local Institution
state: Kerala
city: Mumbai
country: India
facility: Local Institution
state: Maharajhsra
city: Hyderabad
country: India
facility: Local Institution
city: Visakhapatnam
country: India
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
state: Sungdong-Gu
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Mexico City
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Metepec
country: Mexico
facility: Local Institution
state: Estado De Mexico
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Merida
country: Mexico
facility: Local Institution
state: Yucatan
city: Aguascalientes
country: Mexico
facility: Local Institution
city: San Luis Potosi
country: Mexico
facility: Local Institution
city: Bydgoszcz
country: Poland
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution
city: Wroclaw
country: Poland
facility: Local Institution
city: Ekaterinburg
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Yaroslaval
country: Russian Federation
facility: Local Institution
city: Johannesburg
country: South Africa
facility: Local Institution
state: Gauteng
city: Observatory
country: South Africa
facility: Local Institution
state: Western Cape
city: Panorama
country: South Africa
facility: Local Institution
state: Western Cape
city: Kaohsiung
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taoyuan
country: Taiwan
facility: Local Institution
city: Gaziantep
country: Turkey
facility: Local Institution
city: Cambridge
country: United Kingdom
facility: Local Institution
state: Cambridgeshire
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Wolf BJ, Spainhour JC, Arthur JM, Janech MG, Petri M, Oates JC. Development of Biomarker Models to Predict Outcomes in Lupus Nephritis. Arthritis Rheumatol. 2016 Aug;68(8):1955-63. doi: 10.1002/art.39623.
citation: Furie R, Nicholls K, Cheng TT, Houssiau F, Burgos-Vargas R, Chen SL, Hillson JL, Meadows-Shropshire S, Kinaszczuk M, Merrill JT. Efficacy and safety of abatacept in lupus nephritis: a twelve-month, randomized, double-blind study. Arthritis Rheumatol. 2014 Feb;66(2):379-89. doi: 10.1002/art.38260.
citation: Wofsy D, Hillson JL, Diamond B. Comparison of alternative primary outcome measures for use in lupus nephritis clinical trials. Arthritis Rheum. 2013 Jun;65(6):1586-91. doi: 10.1002/art.37940.
citation: Wofsy D, Hillson JL, Diamond B. Abatacept for lupus nephritis: alternative definitions of complete response support conflicting conclusions. Arthritis Rheum. 2012 Nov;64(11):3660-5. doi: 10.1002/art.34624.