Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00430677




Registration number
NCT00430677
Ethics application status
Date submitted
1/02/2007
Date registered
2/02/2007
Date last updated
20/03/2015

Titles & IDs
Public title
Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis
Scientific 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)
Secondary ID [1] 0 0
IM101-075
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Lupus Erythematosus 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Corticosteroids (prednisone or prednisolone)
Treatment: Drugs - Abatacept
Treatment: Drugs - Abatacept
Treatment: Drugs - Mycophenolate mofetil (MMF)
Treatment: Drugs - Abatacept

Experimental: Abatacept 30 mg/kg+Corticosteroids+MMF - Short-term Period

Experimental: Abatacept 10 mg/kg+Corticosteroids+MMF - Short-term Period

Experimental: Placebo+Corticosteroids+MMF - Short-term Period

Experimental: Abatacept 10mg/kg - Long-term Extension Period


Treatment: Drugs: Corticosteroids (prednisone or prednisolone)
tablets, oral, 0.5-0.8 mg/kg, daily

Treatment: Drugs: Abatacept
intravenous solution, injectable, 30 mg/kg, every 28 days

Treatment: Drugs: Abatacept
intravenous solution, injectable, 10 mg/kg, every 28 days

Treatment: Drugs: Mycophenolate mofetil (MMF)
tablets, oral, 1.5 to 2 g, daily

Treatment: Drugs: Abatacept
intravenous solution, injectable, 10 mg/kg, every 28 days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to First Confirmed Complete Renal Response (CRR) During the Short-term (Double-blind) Period
Timepoint [1] 0 0
Day 1 (randomization) to 12 months.
Secondary outcome [1] 0 0
Number of Participants With Confirmed Complete Renal Response (CRR) During Short-term Period
Timepoint [1] 0 0
Day 1 to 12 months
Secondary outcome [2] 0 0
Participants Achieving a Confirmed Complete Renal Response (CRR) at Month 12 During Short-term Period
Timepoint [2] 0 0
At Month 12 from Day 1
Secondary outcome [3] 0 0
Time to Achieve First Confirmed Renal Improvement (RI) During Short-term Period (as Determined by Kaplan-Meier Methodology)
Timepoint [3] 0 0
Day 1 (randomization) to 12 months.
Secondary outcome [4] 0 0
Participants Achieving Renal Improvement (RI) or CRR at Month 12 During Short-term Period
Timepoint [4] 0 0
At Month 12 from Day 1
Secondary outcome [5] 0 0
Number of Months CRR Was Maintained During Short-term Period
Timepoint [5] 0 0
Day 1 (randomization) to 12 Months
Secondary outcome [6] 0 0
Baseline Renal Function Over Time During Short-term Period
Timepoint [6] 0 0
Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365
Secondary outcome [7] 0 0
Change in Renal Function From Baseline Over Time During Short-term Period
Timepoint [7] 0 0
Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365
Secondary outcome [8] 0 0
Baseline and Post Baseline Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index During Short-term Period
Timepoint [8] 0 0
Baseline (Day 1), Post baseline (Month 12 or 28 days after last dose)
Secondary outcome [9] 0 0
Number of Participants Achieving Renal Response (RR) at Month 12 During Short-term Period
Timepoint [9] 0 0
Month 12
Secondary outcome [10] 0 0
Change in SLICC/ACR Damage Index From Baseline During Short-term Period
Timepoint [10] 0 0
Baseline (Day 1), Postbaseline (Month 12 or 28 days after last dose)
Secondary outcome [11] 0 0
Baseline Physical Component Summary of the Short Form (SF)-36 During Short-term Period
Timepoint [11] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [12] 0 0
Change From Baseline in Physical Component Summary of the SF-36 During Short-term Period
Timepoint [12] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [13] 0 0
Baseline Mental Component Summary of the Short SF-36 During Short-term Period
Timepoint [13] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [14] 0 0
Change From Baseline in Mental Component Summary of the SF-36 During Short-term Period
Timepoint [14] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [15] 0 0
Baseline Fatigue as Measured by the Fatigue Visual Analog Scale During Short-term Period
Timepoint [15] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [16] 0 0
Change in Fatigue From Baseline as Measured by the Fatigue Visual Analog Scale During Short-term Period
Timepoint [16] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [17] 0 0
Baseline Fatigue as Measured by Fatigue Severity Scale-Krupp During Short-term Period
Timepoint [17] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [18] 0 0
Change in Fatigue From Baseline as Measured by Fatigue Severity Scale-Krupp During Short-term Period
Timepoint [18] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [19] 0 0
Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs Reported During the Short-term Period
Timepoint [19] 0 0
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.
Secondary outcome [20] 0 0
Participants With AEs of Special Interest During the Short-term Period
Timepoint [20] 0 0
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.
Secondary outcome [21] 0 0
Participants With Marked Hematology Abnormalities During the Short-term Period
Timepoint [21] 0 0
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.
Secondary outcome [22] 0 0
Participants With Marked Laboratory Abnormalities During the Short-term Period
Timepoint [22] 0 0
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.
Secondary outcome [23] 0 0
Participants With Marked Liver and Kidney Function Abnormalities During the Short-term Period
Timepoint [23] 0 0
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.
Secondary outcome [24] 0 0
Participants With Marked Abnormalities Urinalysis During the Short-term Period
Timepoint [24] 0 0
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.
Secondary outcome [25] 0 0
Vital Signs Summary During the Short-term Period: Systolic Blood Pressure (SBP)
Timepoint [25] 0 0
0 - 12 Months
Secondary outcome [26] 0 0
Vital Signs Summary During the Short-term Period: Diastolic Blood Pressure (DBP)
Timepoint [26] 0 0
0 - 12 Months
Secondary outcome [27] 0 0
Vital Signs Summary During the Short-term Period: Heart Rate
Timepoint [27] 0 0
0 - 12 Months
Secondary outcome [28] 0 0
Vital Signs Summary During the Short-term Period: Temperature
Timepoint [28] 0 0
0 - 12 Months
Secondary outcome [29] 0 0
Number of Participants With Positive Abatacept-induced Responses (ECL Method) Over Time During the Short-term Period
Timepoint [29] 0 0
Day 169, Day 365
Secondary outcome [30] 0 0
Baseline Quantitative Immunoglobulins During the Short-term Period
Timepoint [30] 0 0
Baseline (Day 1)
Secondary outcome [31] 0 0
Change in Quantitative Immunoglobulin From Baseline During Short-term Period
Timepoint [31] 0 0
Day 365
Secondary outcome [32] 0 0
Number of Participants Achieving Complete Response by ACCESS Definition
Timepoint [32] 0 0
End of short-term period (Day 365) to termination of the long-term extension period
Secondary outcome [33] 0 0
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
Timepoint [33] 0 0
At Day 365 (end of Short-term Period) and Day 645
Secondary outcome [34] 0 0
Mean Change From Baseline in SLICC/ACR Damage Index
Timepoint [34] 0 0
Day 365 to termination of the long-term extension phase
Secondary outcome [35] 0 0
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
Timepoint [35] 0 0
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.
Secondary outcome [36] 0 0
Number of Participants With a Treatment-emergent Seropositive Result During the Long-term Extension Period
Timepoint [36] 0 0
Day 365 to end of long-term extension period
Secondary outcome [37] 0 0
Number of Participants Achieving Renal Response
Timepoint [37] 0 0
At Day 365 (end of short-term period) and Day 645
Secondary outcome [38] 0 0
Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period
Timepoint [38] 0 0
From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period
Secondary outcome [39] 0 0
Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued)
Timepoint [39] 0 0
From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period
Secondary outcome [40] 0 0
Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued)
Timepoint [40] 0 0
From start of study drug on Day 365 to up to 56 days after last dose in the long-term extension period

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2011
Sample size
Target
Accrual to date
Final
423
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Local Institution - Liverpool
Recruitment hospital [2] 0 0
Local Institution - Clayton
Recruitment hospital [3] 0 0
Local Institution - Heidelberg
Recruitment hospital [4] 0 0
Local Institution - Parkville
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Oklahoma
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Argentina
State/province [12] 0 0
Buenos Aires
Country [13] 0 0
Argentina
State/province [13] 0 0
Cordoba
Country [14] 0 0
Argentina
State/province [14] 0 0
Tucuman
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Brazil
State/province [17] 0 0
Goias
Country [18] 0 0
Brazil
State/province [18] 0 0
Parana
Country [19] 0 0
Brazil
State/province [19] 0 0
Rio Grande Do Sul
Country [20] 0 0
Brazil
State/province [20] 0 0
Rio De Janeiro
Country [21] 0 0
Brazil
State/province [21] 0 0
Sao Paulo
Country [22] 0 0
Canada
State/province [22] 0 0
Alberta
Country [23] 0 0
Canada
State/province [23] 0 0
Manitoba
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
China
State/province [26] 0 0
Beijing
Country [27] 0 0
China
State/province [27] 0 0
Guangdong
Country [28] 0 0
China
State/province [28] 0 0
Shanghai
Country [29] 0 0
China
State/province [29] 0 0
Shanxi
Country [30] 0 0
France
State/province [30] 0 0
Creteil Cedex
Country [31] 0 0
France
State/province [31] 0 0
Paris Cedex 13
Country [32] 0 0
France
State/province [32] 0 0
Strasbourg Cedex
Country [33] 0 0
France
State/province [33] 0 0
Toulouse Cedex 4
Country [34] 0 0
Hong Kong
State/province [34] 0 0
Hong Kong
Country [35] 0 0
India
State/province [35] 0 0
Ahmedabad
Country [36] 0 0
India
State/province [36] 0 0
Andhra Pradesh
Country [37] 0 0
India
State/province [37] 0 0
Gujarat
Country [38] 0 0
India
State/province [38] 0 0
Karnataka
Country [39] 0 0
India
State/province [39] 0 0
Kerala
Country [40] 0 0
India
State/province [40] 0 0
Maharajhsra
Country [41] 0 0
India
State/province [41] 0 0
Hyderabad
Country [42] 0 0
India
State/province [42] 0 0
Visakhapatnam
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Sungdong-Gu
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Seoul
Country [45] 0 0
Mexico
State/province [45] 0 0
Distrito Federal
Country [46] 0 0
Mexico
State/province [46] 0 0
Estado De Mexico
Country [47] 0 0
Mexico
State/province [47] 0 0
Jalisco
Country [48] 0 0
Mexico
State/province [48] 0 0
Nuevo Leon
Country [49] 0 0
Mexico
State/province [49] 0 0
Yucatan
Country [50] 0 0
Mexico
State/province [50] 0 0
Aguascalientes
Country [51] 0 0
Mexico
State/province [51] 0 0
San Luis Potosi
Country [52] 0 0
Poland
State/province [52] 0 0
Bydgoszcz
Country [53] 0 0
Poland
State/province [53] 0 0
Gdansk
Country [54] 0 0
Poland
State/province [54] 0 0
Wroclaw
Country [55] 0 0
Russian Federation
State/province [55] 0 0
Ekaterinburg
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Moscow
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Yaroslaval
Country [58] 0 0
South Africa
State/province [58] 0 0
Gauteng
Country [59] 0 0
South Africa
State/province [59] 0 0
Western Cape
Country [60] 0 0
Taiwan
State/province [60] 0 0
Kaohsiung
Country [61] 0 0
Taiwan
State/province [61] 0 0
Taichung
Country [62] 0 0
Taiwan
State/province [62] 0 0
Taipei
Country [63] 0 0
Taiwan
State/province [63] 0 0
Taoyuan
Country [64] 0 0
Turkey
State/province [64] 0 0
Gaziantep
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Cambridgeshire
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Greater London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00430677
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00430677