Clinical trial NCT01714817: Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lupus Nephritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-10-26
Enrollment: 695
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 study is to evaluate (Abatacept) for treatment of lupus nephritis when used on a background of Cellcept (mycophenolate) and prednisone (corticosteroids)


Eligibility 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

Primary outcomes:
measure: Percentage of Participants in Complete Renal Response (CR) of Lupus Glomerulonephritis at Day 365 of the Double-blind Period
timeFrame: Day 365
Secondary outcomes:
measure: Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period
timeFrame: Day 365
measure: Adjusted Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 365 of the Double-blind Period in Nephrotic Participants
timeFrame: Baseline and Day 365
measure: Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Overall Population
timeFrame: Day 1 and Day 365
measure: Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During Year 1 of the Double-blind Period
timeFrame: Day 1 to Day 365
measure: Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period
timeFrame: From Day 1 up to 56 days post last dose in Year 1 of the double-blind period
measure: Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period
timeFrame: Day 365, Day 729
measure: Median Time to Complete Renal Response During the Double-blind Period in All Participants
timeFrame: Day 365, Day 729
measure: Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants
timeFrame: Day 365, Day 729
measure: Median Time to Partial Renal Response During the Double-blind Period in All Participants
timeFrame: Day 365, Day 729
measure: Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants
timeFrame: Day 365, Day 729
measure: Adjusted Mean Change From Baseline in UPCR Over Time
timeFrame: Day 365; Day 729, includes data up to July 1st 2017 when double-blind therapy ended
measure: Median Percent Change From Baseline in UPCR Over Time
timeFrame: Day 365, Day 729
measure: Adjusted Mean Change From Baseline in eGFR Over Time
timeFrame: Day 365, Day 729
measure: Median Time to First Sustained Change to No Response During the Double-blind Period
timeFrame: Day 365, Day 729
measure: Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period
timeFrame: Day 365, Day 729
measure: Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period
timeFrame: Day 1 to Day 729; Day 365 to Day 729
measure: Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion
timeFrame: Days 1 to 365
measure: Cmax: Maximum Observed Serum Concentration Following Participants Receiving Active Abatacept IV
timeFrame: at 1 hour post Day 1 dose and 30 minutes post Day 337 dose
measure: AUC (TAU): Area Under the Serum Concentration Time Curve Over a Dosing Interval
timeFrame: Days 337 to 365
measure: Summary Statistics for Systolic Blood Pressure
timeFrame: Day 1 to Day 729
measure: Summary Statistics for Diastolic Blood Pressure
timeFrame: Day 1 to Day 729
measure: Summary Statistics for Heart Rate
timeFrame: Day 1 to Day 729
measure: Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L)
timeFrame: Day 729
measure: Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L)
timeFrame: Day 729
measure: Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Percentage of Blood)
timeFrame: Day 729
measure: Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L)
timeFrame: Day 729
measure: Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L)
timeFrame: Day 729
measure: Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L)
timeFrame: Day 729
measure: Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period
timeFrame: Day 1 to Day 365; includes data 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
measure: Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period
timeFrame: Day 1 to Day 365; includes data 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
measure: Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period
timeFrame: Day 1 to Day 365; includes data 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
measure: Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period
timeFrame: Day 1 to Day 365; includes data 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
measure: Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period
timeFrame: Day 1 to Day 365; includes data 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
measure: Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension
timeFrame: From the first dose in Year 2 of the double-blind period up to 56 days post last dose
measure: Percentage of Participants in Treatment Failure Over Time During the Double-blind Period
timeFrame: Day 365, Day 729
measure: Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period
timeFrame: Day 365, Day 729
measure: Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period
timeFrame: Day 729
measure: Percentage of Participants in Overall Population in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period
timeFrame: Day 729
measure: Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period
timeFrame: Day 1 to Day 729
measure: Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period
timeFrame: Day 1 to Day 729
measure: Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period
timeFrame: Day 1 to Day 729
measure: Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period
timeFrame: Day 1 to Day 729
measure: Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period
timeFrame: Day 1 to Day 729
measure: Number of Participants With Abatacept Induced Antibody Response Over Time in the Double-blind Period
timeFrame: Day 365, Day 729
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Of Alabama At Birmingham (Uab)
state: Alabama
city: Long Beach
country: United States
facility: Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
state: California
city: San Leandro
country: United States
facility: East Bay Rheumatology Medical Group, Inc.
state: California
city: Farmington
country: United States
facility: University Of Connecticut Health Center
state: Connecticut
city: Miami
country: United States
facility: University Of Miami Miller School Of Medicine
state: Florida
city: Plantation
country: United States
facility: Integral Rheumatology & Immunology Specialists
state: Florida
city: Atlanta
country: United States
facility: Emory University.
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Baton Rouge
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University School Of Medicine
state: Louisiana
city: Boston
country: United States
facility: Brigham & Women'S Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Camden
country: United States
facility: Local Institution
state: New Jersey
city: Brooklyn
country: United States
facility: Suny Downstate Medical Center
state: New York
city: Great Neck
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: New York
country: United States
facility: Hospital For Special Surgery
state: New York
city: New York
country: United States
facility: Local Institution
state: New York
city: Chapel Hill
country: United States
facility: University Of North Carolina At Chapel Hill
state: North Carolina
city: Raleigh
country: United States
facility: Shanahan Rheum & Immunotherapy, PLLC
state: North Carolina
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Middleburg Heights
country: United States
facility: Paramount Medical Research & Consulting, Llc
state: Ohio
city: Knoxville
country: United States
facility: Rheumatology Consultants Pllc
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University Of Utah Hospital
state: Utah
city: Charlottesville
country: United States
facility: Local Institution
state: Virginia
city: Capital Federal
country: Argentina
facility: Organizacion Medica De Investigacion S.A. (Omi)
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Hospital Privado-Centro Medico De Cordoba S.A.
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: Parkville
country: Australia
facility: Local Institution
state: Victoria
city: Perth
country: Australia
facility: Local Institution
state: Western Australia
city: Savaldor
country: Brazil
facility: Local Institution
state: Bahia
city: Goiania
country: Brazil
facility: Local Institution
state: Goias
city: Belo Horizonte
country: Brazil
facility: Local Institution
state: Minas Gerais
city: Juiz De Fora
country: Brazil
facility: Local Institution
state: Minas Gerais
city: Uberlandia
country: Brazil
facility: Local Institution
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Mississauga
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Santiago De Chile
country: Chile
facility: Local Institution
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution
state: Metropolitana
city: Independencia
country: Chile
facility: Local Institution
state: Santiago
city: Vina Del Mar
country: Chile
facility: Local Institution
state: Valparaiso
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: Haikou
country: China
facility: Local Institution
state: Hainan
city: Wuhan
country: China
facility: Local Institution
state: Hebei
city: Harbin
country: China
facility: Local Institution
state: Heilongjiang
city: Zhengzhou
country: China
facility: Local Institution
state: Henan
city: Wuxi
country: China
facility: Local Institution
state: Jiangsu
city: Nanchang
country: China
facility: Local Institution
state: Jiangxi
city: Xian
country: China
facility: Local Institution
state: Shan1xi
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Chengdu
country: China
facility: Local Institution
state: Sichuan
city: Hangzhou
country: China
facility: Local Institution
state: Zhejiang
city: Beijing
country: China
facility: Local Institution
city: Chong Qing
country: China
facility: Local Institution
city: Guangzhou
country: China
facility: Local Institution
city: Nanchang
country: China
facility: Local Institution
city: Nanning
country: China
facility: Local Institution
city: Shanghai
country: China
facility: Local Institution
city: Shanghai
country: China
facility: Local Institution
city: Shanghai
country: China
facility: Local Institution
city: Xi'An
country: China
facility: Local Institution
city: Bogota
country: Colombia
facility: Riesgo De Fractura S.A. Cayre Ips
state: Cundinamarca
city: Bucaramanga
country: Colombia
facility: Servimed E.U
state: Santander
city: Barranquilla
country: Colombia
facility: Clinica De La Costa
city: Barranquilla
country: Colombia
facility: Circaribe S.A.S
city: Bogota
country: Colombia
facility: Hospital Universitario San Ignacio
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Praha 2
country: Czechia
facility: Local Institution
city: Hong Kong
country: Hong Kong
facility: Local Institution
city: Secunderabad
country: India
facility: Local Institution
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Local Institution
state: Gujrat
city: Gurgaon
country: India
facility: Local Institution
city: Hyderabad
country: India
facility: Local Institution
city: Lucknow-
country: India
facility: Local Institution
city: New Delhi
country: India
facility: Local Institution
city: Haifa
country: Israel
facility: Local Institution
city: Haifa
country: Israel
facility: Local Institution
city: Ramat-gan
country: Israel
facility: Local Institution
city: Tel Aviv
country: Israel
facility: Local Institution
city: Brescia
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Padova
country: Italy
facility: Local Institution
city: Reggio Emilia
country: Italy
facility: Local Institution
city: Torino
country: Italy
facility: Local Institution
city: Nagakute-shi
country: Japan
facility: Local Institution
state: Aichi
city: Nagoya-shi
country: Japan
facility: Local Institution
state: Aichi
city: Chiba-shi
country: Japan
facility: Local Institution
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Local Institution
state: Fukuoka
city: Kitakyushu-shi
country: Japan
facility: Local Institution
state: Fukuoka
city: Maebashi-shi
country: Japan
facility: Local Institution
state: Gunma
city: Sapporo-shi
country: Japan
facility: Local Institution
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Local Institution
state: Hokkaido
city: Kanazawa-shi
country: Japan
facility: Local Institution
state: Ishikawa
city: Yokohama-shi
country: Japan
facility: Local Institution
state: Kanagawa
city: Sendai-shi
country: Japan
facility: Local Institution
state: Miyagi
city: Nagasaki-shi
country: Japan
facility: Local Institution
state: Nagasaki
city: Niigata-shi
country: Japan
facility: Local Institution
state: Niigata
city: Okayama-shi
country: Japan
facility: Local Institution
state: Okayama
city: Iruma-gun
country: Japan
facility: Local Institution
state: Saitama
city: Shimotsuke-shi
country: Japan
facility: Local Institution
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Local Institution
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Local Institution
state: Tokyo
city: Chuo-ku
country: Japan
facility: Local Institution
state: Tokyo
city: Fuchu
country: Japan
facility: Local Institution
state: Tokyo
city: Ota-ku
country: Japan
facility: Local Institution
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Kita-gun
country: Japan
facility: Local Institution
city: Osaka
country: Japan
facility: Local Institution
city: Daegu
country: Korea, Republic of
facility: Local Institution
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 Fededral
city: Mexico City
country: Mexico
facility: Hospital De Jesus
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Hospital General De Mexico O.D.
state: Distrito Federal
city: Guadalajara, Jalisco
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Centro De Est D Inv. Basica Y Clinica
state: Jalisco
city: Merida
country: Mexico
facility: Centro Medico De Las Americas
state: Yucatan
city: Distrito Federal
country: Mexico
facility: Instituto Nacional De Ciencias Medicas Y Nutricion S.Z.
city: San Luis Potosi
country: Mexico
facility: Centro Potosino de Inv Clinica
city: San Luis Potosi
country: Mexico
facility: Hosp Central I.Morones Prieto
city: Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen
city: Lima
country: Peru
facility: Hospital Nacional Cayetano Heredia
city: Lima
country: Peru
facility: Instituto De Ginecologia Y Reproduccion Inv. Clinical Sac
city: San Juan
country: Puerto Rico
facility: Local Institution
city: Bucharest
country: Romania
facility: Local Institution
city: Bucuresti
country: Romania
facility: Local Institution
city: Bucuresti
country: Romania
facility: Local Institution
city: Cluj-napoca
country: Romania
facility: Local Institution
city: Iasi
country: Romania
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: Ufa
country: Russian Federation
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Kaohsiung
country: Taiwan
facility: Local Institution
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: Antalya
country: Turkey
facility: Local Institution
city: Edirne
country: Turkey
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: